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Genomic newborn screening: BabyScreen+ v1.116 CLN8 Melanie Marty reviewed gene: CLN8: Rating: GREEN; Mode of pathogenicity: None; Publications: 16570191, 15024724; Phenotypes: Ceroid lipofuscinosis, neuronal, 8, MIM# 600143, Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant, MIM# 610003; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.113 GCH1 Lilian Downie reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301681; Phenotypes: Dystonia, DOPA-responsive MIM#128230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.111 LIG4 Santosh Varughese reviewed gene: LIG4: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 16088910, 9823897, 10911993, 15333585, 9809069, 12023982, 11040211, 15175260, 19451691, 17554302, 11779494; Phenotypes: LIG4 SYNDROME, MULTIPLE MYELOMA, RESISTANCE TO; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.110 ELANE Zornitza Stark commented on gene: ELANE: ClinGen: there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).
Genomic newborn screening: BabyScreen+ v1.108 CBS Zornitza Stark Classified gene: CBS as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.108 CBS Zornitza Stark Gene: cbs has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.107 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.105 WNK1 Zornitza Stark Classified gene: WNK1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.105 WNK1 Zornitza Stark Gene: wnk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.104 TRIM28 Zornitza Stark Classified gene: TRIM28 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.104 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.103 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to BabyScreen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Established gene-disease association, more than 10 individuals reported.

Onset in childhood.

Included for completeness as managed similarly to WT1.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.102 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.102 TRHR Zornitza Stark Phenotypes for gene: TRHR were changed from Thyrotropin-releasing hormone resistance, generalized to Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573
Genomic newborn screening: BabyScreen+ v1.100 TRHR Zornitza Stark Classified gene: TRHR as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.100 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.99 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.99 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.98 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.97 SCNN1G Zornitza Stark Classified gene: SCNN1G as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.97 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.96 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.94 RPS7 Zornitza Stark Classified gene: RPS7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.94 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.93 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.91 RPL35A Zornitza Stark Classified gene: RPL35A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.91 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.90 REST Zornitza Stark Classified gene: REST as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.90 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.89 REST Zornitza Stark gene: REST was added
gene: REST was added to BabyScreen+ newborn screening. Sources: Expert list
cancer, treatable tags were added to gene: REST.
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: Established association, more than 10 families reported.

Childhood onset.

Included for completeness as managed similarly to WT1.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.88 PSTPIP1 Zornitza Stark Classified gene: PSTPIP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.88 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.86 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.84 PPOX Zornitza Stark Classified gene: PPOX as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.84 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.83 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.83 POMC Zornitza Stark Phenotypes for gene: POMC were changed from Proopiomelanocortin deficiency to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Genomic newborn screening: BabyScreen+ v1.82 POMC Zornitza Stark Classified gene: POMC as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.82 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.81 POMC Zornitza Stark reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.81 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.81 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.80 POLE Zornitza Stark gene: POLE was added
gene: POLE was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: POLE.
Mode of inheritance for gene: POLE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLE were set to IMAGE-I syndrome, MIM# 618336
Review for gene: POLE was set to GREEN
Added comment: Established gene-disease association.

Multi-system disorder comprising GH and adrenal hypoplasia.

Treatment: hydrocortisone

non-genetic confirmatory testing: hormone levels
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.79 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.79 NCF4 Zornitza Stark Phenotypes for gene: NCF4 were changed from Chronic granulomatous disease 3, autosomal recessive, MIM# 613960; Chronic granulomatous disease to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
Genomic newborn screening: BabyScreen+ v1.78 NCF4 Zornitza Stark Classified gene: NCF4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.78 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.77 NCF4 Zornitza Stark reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.77 LPL Zornitza Stark Classified gene: LPL as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.77 LPL Zornitza Stark Gene: lpl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.75 LAT Zornitza Stark Classified gene: LAT as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.75 LAT Zornitza Stark Gene: lat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.73 KLHL3 Zornitza Stark Classified gene: KLHL3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.73 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.72 KLHL3 Zornitza Stark gene: KLHL3 was added
gene: KLHL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: KLHL3.
Mode of inheritance for gene: KLHL3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: KLHL3 were set to Pseudohypoaldosteronism, type IID, MIM# 614495
Review for gene: KLHL3 was set to GREEN
Added comment: Established gene disease association.

Results in hyperkalaemia and later, the development of hypertension.

Treatment: thiazide diuretics normalise electrolytes

Non-genetic confirmatory testing: electrolytes
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.71 IRF8 Zornitza Stark Classified gene: IRF8 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.71 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.70 IRF8 Zornitza Stark gene: IRF8 was added
gene: IRF8 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IRF8.
Mode of inheritance for gene: IRF8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRF8 were set to Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990
Review for gene: IRF8 was set to GREEN
Added comment: At least 4 families reported with bi-allelic variants. Gene-disease association also proposed for mono-allelic variants but only two individuals reported.

Recurrent infections presenting in infancy.

Treatment: BMT

Non-genetic confirmatory testing available
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.69 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.69 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from Inflammatory bowel disease; Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567 to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
Genomic newborn screening: BabyScreen+ v1.68 IL10RB Zornitza Stark Classified gene: IL10RB as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.68 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.67 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.67 IL10 Zornitza Stark Classified gene: IL10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.67 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.65 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.64 IGF1 Zornitza Stark Classified gene: IGF1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.64 IGF1 Zornitza Stark Gene: igf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.63 GALNT3 Zornitza Stark Classified gene: GALNT3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.63 GALNT3 Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.62 GALNT3 Zornitza Stark gene: GALNT3 was added
gene: GALNT3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: GALNT3.
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT3 were set to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900
Review for gene: GALNT3 was set to GREEN
Added comment: Established gene-disease association.

Onset in infancy/childhood.

Treatment: dietary restriction, phosphate binders, acetazolamide

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.61 FECH Zornitza Stark Classified gene: FECH as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.61 FECH Zornitza Stark Gene: fech has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.60 FECH Zornitza Stark gene: FECH was added
gene: FECH was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, haematological tags were added to gene: FECH.
Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FECH were set to Protoporphyria, erythropoietic, 1, MIM# 177000
Review for gene: FECH was set to GREEN
Added comment: Established gene-disease association.

Onset of photosensitivity is in infancy/childhood.

Treatment: Afamelanotide

Non-genetic confirmatory testing: free protoporphyrin
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.59 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.58 F13B Zornitza Stark Classified gene: F13B as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.58 F13B Zornitza Stark Gene: f13b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.57 F10 Zornitza Stark Classified gene: F10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.57 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.56 F10 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity: for review. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex); to: Well established gene-disease association.

Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally hemarthrosis.

Treatment: plasma-derived factor 10 concentrate (Coagadex)
Genomic newborn screening: BabyScreen+ v1.56 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.55 ERCC4 Zornitza Stark Classified gene: ERCC4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.55 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.54 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.54 CYP7B1 Zornitza Stark Phenotypes for gene: CYP7B1 were changed from Cholestasis, severe to Bile acid synthesis defect, congenital, 3, MIM# 613812
Genomic newborn screening: BabyScreen+ v1.52 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.52 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.51 CYP7B1 Zornitza Stark reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24658845, 31337596, 30366773, 9802883; Phenotypes: Bile acid synthesis defect, congenital, 3, MIM# 613812; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.51 CUL3 Zornitza Stark Classified gene: CUL3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.51 CUL3 Zornitza Stark Gene: cul3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.50 CUL3 Zornitza Stark gene: CUL3 was added
gene: CUL3 was added to BabyScreen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: CUL3.
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CUL3 were set to Pseudohypoaldosteronism, type IIE 614496
Review for gene: CUL3 was set to GREEN
Added comment: Established gene-disease association.

Variants in this gene also cause a neurodevelopmental disorder; however, there is some genotype-phenotype correlation literature to help distinguish the two.

Results in hyperkalaemia and development of hypertension. However, the onset of hypertension is generally later in life.

Treatment: thiazide diuretics normalise biochemical abnormalities
Sources: Expert list
Genomic newborn screening: BabyScreen+ v1.48 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.47 COQ6 Zornitza Stark Classified gene: COQ6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.47 COQ6 Zornitza Stark Gene: coq6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.46 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.45 COQ2 Zornitza Stark Classified gene: COQ2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.45 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.44 CHRNB1 Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.44 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.43 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.42 CFI Zornitza Stark Classified gene: CFI as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.42 CFI Zornitza Stark Gene: cfi has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.41 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.40 CFH Zornitza Stark Classified gene: CFH as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.40 CFH Zornitza Stark Gene: cfh has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.39 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.37 CFD Zornitza Stark Classified gene: CFD as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.37 CFD Zornitza Stark Gene: cfd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.36 CEBPE Zornitza Stark Classified gene: CEBPE as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.36 CEBPE Zornitza Stark Gene: cebpe has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.34 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.33 C3 Zornitza Stark Classified gene: C3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.33 C3 Zornitza Stark Gene: c3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.32 C2 Zornitza Stark Classified gene: C2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.32 C2 Zornitza Stark Gene: c2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.30 APOA5 Zornitza Stark Gene: apoa5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.29 AP3D1 Zornitza Stark Classified gene: AP3D1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.29 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.27 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.27 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from Alpha-methylacyl-CoA racemase deficiency; Bile acid synthesis defect, congenital, 4 to Bile acid synthesis defect, congenital, 4, MIM# 214950
Genomic newborn screening: BabyScreen+ v1.25 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.25 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.24 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12512044; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v1.23 TRAC Zornitza Stark Gene: trac has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.23 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to BabyScreen+ newborn screening. Sources: Expert Review
founder, technically challenging tags were added to gene: TRAC.
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAC were set to 21206088
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, MIM#615387
Review for gene: TRAC was set to RED
Added comment: Single variant reported to date in 6 patients; 2 unrelated children from consanguineous families of Pakistani descent (PMID: 21206088); 1 non-consanguineous family from North-west India (PMID: 33909184) and 1 consanguineous parents of East Indian (https://lymphosign.com/doi/10.14785/lymphosign-2022-0001)

Also note annotation issues in certain variant curation and annotation tools.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v1.22 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.22 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.21 IGHM Zornitza Stark Classified gene: IGHM as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.21 IGHM Zornitza Stark Gene: ighm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.20 NCF1 Zornitza Stark Classified gene: NCF1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.20 NCF1 Zornitza Stark Gene: ncf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.19 NCF1 Zornitza Stark Classified gene: NCF1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.19 NCF1 Zornitza Stark Gene: ncf1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.18 CYP21A2 Zornitza Stark Classified gene: CYP21A2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v1.18 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.17 PMS2 Zornitza Stark Classified gene: PMS2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.17 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.16 IGHM Zornitza Stark Classified gene: IGHM as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.16 IGHM Zornitza Stark Gene: ighm has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.15 STRC Zornitza Stark Classified gene: STRC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v1.15 STRC Zornitza Stark Gene: strc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.14 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.13 KCNA5 Zornitza Stark Classified gene: KCNA5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.13 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.12 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.12 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.11 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.11 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from Dyskeratosis congenita, X-linked, MIM# 305000; Dyskeratosis congenita to Dyskeratosis congenita, X-linked, MIM# 305000
Genomic newborn screening: BabyScreen+ v1.10 DKC1 Zornitza Stark Classified gene: DKC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.10 DKC1 Zornitza Stark Gene: dkc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.9 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyskeratosis congenita, X-linked, MIM# 305000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v1.9 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.8 CDKN2A Zornitza Stark Classified gene: CDKN2A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.8 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.7 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.7 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from Pulmonary hypertension, familial primary to Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600
Genomic newborn screening: BabyScreen+ v1.6 BMPR2 Zornitza Stark Classified gene: BMPR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.6 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.5 BMPR2 Zornitza Stark reviewed gene: BMPR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary hypertension, familial primary, 1, with or without HHT, MIM# 178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v1.5 AIP Zornitza Stark Classified gene: AIP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.5 AIP Zornitza Stark Gene: aip has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.4 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.3 PHOX2B Zornitza Stark Classified gene: PHOX2B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v1.3 PHOX2B Zornitza Stark Gene: phox2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v1.2 AIP Zornitza Stark Gene: aip has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v1.2 AIP Zornitza Stark Phenotypes for gene: AIP were changed from Pituitary adenoma to Pituitary adenoma predisposition, MIM# 102200
Genomic newborn screening: BabyScreen+ v1.1 AIP Zornitza Stark reviewed gene: AIP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary adenoma predisposition, MIM# 102200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v1.0 Zornitza Stark promoted panel to version 1.0
Genomic newborn screening: BabyScreen+ v0.2178 DMD Zornitza Stark Classified gene: DMD as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2178 DMD Zornitza Stark Gene: dmd has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2176 COL4A6 Zornitza Stark Classified gene: COL4A6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2176 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2175 COL4A6 Zornitza Stark edited their review of gene: COL4A6: Added comment: Further review of PMID:33840813;

Family A:
- Proband is hemi for COL4A6 and het for GJB2. Mother is het for COL4A6
- hypothesised that in the proband is more severe than the parents due to additive effects of his two variants however, mother's audiometric data was unavailable to confirm this.

Family B:
- Variant does not segregate within family with the proband being WT in this gene
- NM_001287758.1: c.3272G>C is the mutation however, it appears to be an annotation error as it corresponds to NC_000023.11:g.108171443 in GRCh38. At that position, the c. is T not G and the amino acid residue is Val, not Gly.

In addition, there is a missense affecting Gly of GXY in gnomad v3 with 38 hemis.; Changed rating: RED; Changed publications: 33840813; Changed phenotypes: Deafness, X-linked 6 MIM#300914; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.2175 MT-RNR1 Zornitza Stark changed review comment from: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G
m.1005T>C
m.1095T>C

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review; to: The following variants have been associated with aminoglycoside-induced deafness:
m.1555A>G and m.1494C>T

Alerts can be placed in medical records to avoid aminoglycoside administration.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2175 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Classified gene: PDP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2174 PDP1 Zornitza Stark Gene: pdp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Classified gene: DLAT as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2173 DLAT Zornitza Stark Gene: dlat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2172 DLAT Zornitza Stark gene: DLAT was added
gene: DLAT was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DLAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DLAT were set to Pyruvate dehydrogenase E2 deficiency, MIM# 245348
Review for gene: DLAT was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Classified gene: PDHB as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2171 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2170 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, metabolic tags were added to gene: PDHB.
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM# 614111
Review for gene: PDHB was set to GREEN
Added comment: Well established gene-disease association.

Clinical presentation is in infancy.

Treatment: ketogenic diet has a significant impact on outcome; some cases responsive to thiamine

Non-genetic confirmatory testing: enzymology

Included for consistency with PDHA1/PDHX
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Classified gene: TUBB4B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2169 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Classified gene: SUFU as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2168 SUFU Zornitza Stark Gene: sufu has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Classified gene: SLITRK6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2167 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Classified gene: PAX5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2166 PAX5 Zornitza Stark Gene: pax5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Classified gene: MPZL2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2165 MPZL2 Zornitza Stark Gene: mpzl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Classified gene: LMX1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2164 LMX1A Zornitza Stark Gene: lmx1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Classified gene: GREB1L as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2163 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Classified gene: NLRP3 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2162 NLRP3 Zornitza Stark Gene: nlrp3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2161 NLRP3 Zornitza Stark gene: NLRP3 was added
gene: NLRP3 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: NLRP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NLRP3 were set to 25038238
Phenotypes for gene: NLRP3 were set to Familial cold inflammatory syndrome 1, MIM#120100 Muckle-Wells syndrome, MIM#191900 CINCA syndrome, MIM#607115 Deafness, autosomal dominant 34, with or without inflammation, MIM#617772 Keratoendothelitis fugax hereditaria, MIM#148200
Review for gene: NLRP3 was set to AMBER
Added comment: Established gene-disease associations.

Variants in this gene cause a spectrum of clinical phenotypes, ranging from onset in infancy to adult-onset, with variable severity. Genotype-phenotype correlation is unclear, hence not suitable for inclusion at this time.

Treatment: corticosteroids, anakinra, rilonacept and canakinumab.

Non-genetic confirmatory testing: no.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2159 AMT Zornitza Stark Classified gene: AMT as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2159 AMT Zornitza Stark Gene: amt has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2158 AMT Zornitza Stark edited their review of gene: AMT: Added comment: Severe infantile forms: treatment does not currently alter outcomes.

Attenuated forms can have onset in childhood, therapy with sodium benzoate and NMDA (The N-methyl-D-aspartate receptor) receptor site antagonists (dextromethorphan, ketamine) but uncertainty about effectiveness.; Changed rating: AMBER; Changed publications: 35683414
Genomic newborn screening: BabyScreen+ v0.2157 GLDC Zornitza Stark Classified gene: GLDC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2157 GLDC Zornitza Stark Gene: gldc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark Classified gene: GLDC as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2156 GLDC Zornitza Stark Gene: gldc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2155 SAMHD1 Zornitza Stark Classified gene: SAMHD1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2155 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2154 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2154 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Classified gene: SGSH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2152 SGSH Zornitza Stark Gene: sgsh has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2151 SGSH Zornitza Stark reviewed gene: SGSH: Rating: AMBER; Mode of pathogenicity: None; Publications: 31044143; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2151 GPR161 Zornitza Stark Gene: gpr161 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2151 GPR161 Zornitza Stark Classified gene: GPR161 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2151 GPR161 Zornitza Stark Gene: gpr161 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2150 CTR9 Zornitza Stark Gene: ctr9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2150 CTR9 Zornitza Stark Classified gene: CTR9 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2150 CTR9 Zornitza Stark Gene: ctr9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2149 ALK Zornitza Stark Gene: alk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2149 ALK Zornitza Stark Classified gene: ALK as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2149 ALK Zornitza Stark Gene: alk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2148 GPR161 Lilian Downie gene: GPR161 was added
gene: GPR161 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GPR161 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GPR161 were set to PMID: 31609649
Phenotypes for gene: GPR161 were set to Medulloblastoma predisposition syndrome MIM#155255
Penetrance for gene: GPR161 were set to Incomplete
Review for gene: GPR161 was set to RED
Added comment: Increased risk of medulloblastoma at <3yrs
Also identified in population and healthy parents
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2148 CTR9 Lilian Downie gene: CTR9 was added
gene: CTR9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to PMID: 32412586
Phenotypes for gene: CTR9 were set to Wilms tumour predisposition
Penetrance for gene: CTR9 were set to Incomplete
Review for gene: CTR9 was set to RED
Added comment: 9/14 germline variant developed Wilms (in 4 families)
Red due to reduced penetrance
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2148 TUBB4B Lilian Downie gene: TUBB4B was added
gene: TUBB4B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to PMID: 29198720, 35240325
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness MIM#617879
Review for gene: TUBB4B was set to RED
Added comment: The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness
Not consistently hearing phenotype <5years therefore excluded
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2148 MPZL2 Lilian Downie gene: MPZL2 was added
gene: MPZL2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: MPZL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPZL2 were set to PMID: 29982980, 29961571, 35734045,33234333
Phenotypes for gene: MPZL2 were set to Deafness, autosomal recessive 111 MIM#618145
Review for gene: MPZL2 was set to RED
Added comment: Most cases are pre-lingual but 29961571, 35734045 report adult onset so I think should be excluded based on variability of age of onset
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2148 CRYM Zornitza Stark Gene: crym has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2148 CRYM Zornitza Stark Classified gene: CRYM as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2148 CRYM Zornitza Stark Gene: crym has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2147 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2147 COL4A6 Zornitza Stark Classified gene: COL4A6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2147 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2146 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2146 CLDN9 Zornitza Stark Classified gene: CLDN9 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2146 CLDN9 Zornitza Stark Gene: cldn9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2145 CEP250 Zornitza Stark Gene: cep250 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2145 CEP250 Zornitza Stark Classified gene: CEP250 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2145 CEP250 Zornitza Stark Gene: cep250 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2144 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2144 ABHD12 Zornitza Stark Classified gene: ABHD12 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2144 ABHD12 Zornitza Stark Gene: abhd12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2143 CD164 Zornitza Stark Gene: cd164 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2143 CD164 Zornitza Stark Classified gene: CD164 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2143 CD164 Zornitza Stark Gene: cd164 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2142 AP1B1 Zornitza Stark Gene: ap1b1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2142 AP1B1 Zornitza Stark Classified gene: AP1B1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2142 AP1B1 Zornitza Stark Gene: ap1b1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2141 AP1B1 Zornitza Stark reviewed gene: AP1B1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Keratitis-ichthyosis-deafness syndrome, autosomal recessive MIM#242150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2141 GREB1L Lilian Downie gene: GREB1L was added
gene: GREB1L was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to PMID: 29955957, 32585897
Phenotypes for gene: GREB1L were set to Deafness, autosomal dominant 80 MIM#619274
Review for gene: GREB1L was set to GREEN
Added comment: Congenital hearing impairment with cochlear abnormalities
This gene also causes Renal hypodysplasia/aplasia 3 MIM#617805 with no clear difference in mutation spectrum
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 COL4A6 Lilian Downie gene: COL4A6 was added
gene: COL4A6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: COL4A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: COL4A6 were set to PMID: 33840813, PMID: 23714752
Phenotypes for gene: COL4A6 were set to Deafness, X-linked 6 MIM#300914
Review for gene: COL4A6 was set to GREEN
Added comment: Pre-lingual or congenital deafness in males
consider not reporting in females (may have adult onset hearing impairment)
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 CLDN9 Lilian Downie gene: CLDN9 was added
gene: CLDN9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CLDN9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN9 were set to PMID: 34265170
Phenotypes for gene: CLDN9 were set to Deafness, autosomal recessive 116 MIM#619093
Review for gene: CLDN9 was set to RED
Added comment: Age of onset not consistently <5
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 ABHD12 Lilian Downie gene: ABHD12 was added
gene: ABHD12 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABHD12 were set to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674
Review for gene: ABHD12 was set to RED
Added comment: Age of onset not consistently under 5 for treatable elements such as hearing loss.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 CD164 Lilian Downie gene: CD164 was added
gene: CD164 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CD164 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CD164 were set to Deafness, autosomal dominant 66 MIM#616969
Review for gene: CD164 was set to RED
Added comment: Green in our mendeliome/deafness but limited evidence by clingen
variable age of onset from newborn to 20's reason for exclusion
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 AP1B1 Lilian Downie gene: AP1B1 was added
gene: AP1B1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1B1 were set to PMID:31630791, 31630788, 33452671
Phenotypes for gene: AP1B1 were set to Keratitis-ichthyosis-deafness syndrome, autosomal recessive MIM#242150
Review for gene: AP1B1 was set to GREEN
Added comment: Icthyosis
progressive hearing loss (childhood) often detected newborn screening
photophobia
corneal scarring/keratitis
variable dev delay
part of copper metabolism pathway but no proven treatment
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2141 LAMP2 Zornitza Stark Classified gene: LAMP2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2141 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2138 MYH7 Zornitza Stark Classified gene: MYH7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2138 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2137 MYH7 Zornitza Stark edited their review of gene: MYH7: Added comment: Discussed with paedric cardiologist: include bi-allelic cardiac variants as can present in the neonatal period with an aggressive cardiomyopathy and associated arrhythmias.; Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, hypertrophic, 1, MIM# 192600; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2136 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2136 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2135 TRDN Zornitza Stark Classified gene: TRDN as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2135 TRDN Zornitza Stark Gene: trdn has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2134 TRDN Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Genomic newborn screening: BabyScreen+ v0.2134 TECRL Zornitza Stark Classified gene: TECRL as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2134 TECRL Zornitza Stark Gene: tecrl has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2133 TECRL Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Genomic newborn screening: BabyScreen+ v0.2133 SCN5A Zornitza Stark Classified gene: SCN5A as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2133 SCN5A Zornitza Stark Gene: scn5a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2132 PRKG1 Zornitza Stark Classified gene: PRKG1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2132 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2131 PRKG1 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).

Discussed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.2131 MYH11 Zornitza Stark Classified gene: MYH11 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2131 MYH11 Zornitza Stark Gene: myh11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2130 MYH11 Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 12 individuals with MYH11 pathogenic variants indicated that 34% had an aortic dissection and one individual (8%) underwent prophylactic aortic aneurysm repair.

Reviewed with a paediatric cardiologist: variable penetrance and age of onset, does not meet criteria for gNBS.
Genomic newborn screening: BabyScreen+ v0.2130 LOX Zornitza Stark Classified gene: LOX as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2130 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2129 LOX Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.

Discussed with paediatric cardiologist: variable penetrance and age of onset, does not fit with criteria for gNBS.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.2129 JUP Zornitza Stark Classified gene: JUP as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2129 JUP Zornitza Stark Gene: jup has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2128 DSP Zornitza Stark Classified gene: DSP as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2128 DSP Zornitza Stark Gene: dsp has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2127 CASQ2 Zornitza Stark Classified gene: CASQ2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2127 CASQ2 Zornitza Stark Gene: casq2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2126 CALM1 Zornitza Stark Classified gene: CALM1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2126 CALM1 Zornitza Stark Gene: calm1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2124 CALM3 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Exclude for CPVT: association has moderate evidence, there are issues with penetrance, and treatment is generally only recommended in symptomatic individuals.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.2124 CALM2 Zornitza Stark Classified gene: CALM2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2124 CALM2 Zornitza Stark Gene: calm2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2123 CALM2 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
Genomic newborn screening: BabyScreen+ v0.2123 CALM1 Zornitza Stark changed review comment from: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen; to: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

Reviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.
Genomic newborn screening: BabyScreen+ v0.2123 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2120 VAMP1 Zornitza Stark Classified gene: VAMP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2120 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2119 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2119 TUBB1 Zornitza Stark Classified gene: TUBB1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2119 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2117 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2117 SLC26A7 Zornitza Stark Classified gene: SLC26A7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2117 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2115 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2115 OTX2 Zornitza Stark Classified gene: OTX2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2115 OTX2 Zornitza Stark Gene: otx2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2113 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2113 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from Septooptic dysplasia, MIM# 182230; Pituitary hypoplasia to Pituitary hormone deficiency, combined, 5, MIM# 182230
Genomic newborn screening: BabyScreen+ v0.2111 HESX1 Zornitza Stark Classified gene: HESX1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2111 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2110 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2110 CDCA8 Zornitza Stark Classified gene: CDCA8 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2110 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2108 FOXN1 Zornitza Stark Gene: foxn1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2108 FOXN1 Zornitza Stark Phenotypes for gene: FOXN1 were changed from Congenital alopecia with T-cell immunodeficiency; T-cell immunodeficiency, congenital alopecia, and nail dystrophy , MIM#601705; T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM# 618806 to T-cell immunodeficiency, congenital alopecia, and nail dystrophy, autosomal recessive MIM# 601705; T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM#t 618806
Genomic newborn screening: BabyScreen+ v0.2105 FOXN1 Zornitza Stark Classified gene: FOXN1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2105 FOXN1 Zornitza Stark Gene: foxn1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2104 FOXN1 Zornitza Stark reviewed gene: FOXN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31447097, 18339010, 10206641; Phenotypes: T-cell immunodeficiency, congenital alopecia, and nail dystrophy, autosomal recessive MIM# 601705, T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant, MIM#t 618806; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2104 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2104 TMEM38B Zornitza Stark Classified gene: TMEM38B as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2104 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2103 TMEM38B Zornitza Stark gene: TMEM38B was added
gene: TMEM38B was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM38B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM38B were set to 23054245; 28323974
Phenotypes for gene: TMEM38B were set to Osteogenesis imperfecta, type XIV , MIM#615066
Review for gene: TMEM38B was set to GREEN
Added comment: More than 10 families reported.

Variable severity, onset of fractures generally in infancy.

Treatment: bisphosphanates; improvement in BMD reported.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2102 SPARC Zornitza Stark Gene: sparc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2102 SPARC Zornitza Stark gene: SPARC was added
gene: SPARC was added to Baby Screen+ newborn screening. Sources: Expert list
skeletal tags were added to gene: SPARC.
Mode of inheritance for gene: SPARC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPARC were set to 26027498; 34462290
Phenotypes for gene: SPARC were set to Osteogenesis imperfecta, type XVII, MIM# 616507
Review for gene: SPARC was set to RED
Added comment: Established gene-disease association, 5 families reported.

Onset of fractures in infancy.

Prominent neuromuscular features, MRI brain changes; some with ID.

Treatment: bisphosphanates are generally used in OI but the case reports where these have been used do not seem terribly convincing in terms of response/improvement.

Exclude for now.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2101 SP7 Zornitza Stark Gene: sp7 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2101 SP7 Zornitza Stark Phenotypes for gene: SP7 were changed from Osteogenesis imperfecta, type XII to Osteogenesis imperfecta, type XII, MIM# 613849
Genomic newborn screening: BabyScreen+ v0.2098 SP7 Zornitza Stark Classified gene: SP7 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2098 SP7 Zornitza Stark Gene: sp7 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2097 SP7 Zornitza Stark reviewed gene: SP7: Rating: AMBER; Mode of pathogenicity: None; Publications: 36881265; Phenotypes: Osteogenesis imperfecta, type XII, MIM# 613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2097 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2097 SERPINH1 Zornitza Stark Classified gene: SERPINH1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2097 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2096 SERPINH1 Zornitza Stark gene: SERPINH1 was added
gene: SERPINH1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: SERPINH1.
Mode of inheritance for gene: SERPINH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINH1 were set to 29520608; 25510505; 33524049
Phenotypes for gene: SERPINH1 were set to Osteogenesis imperfecta, type X, MIM# 613848
Review for gene: SERPINH1 was set to GREEN
Added comment: Established gene-disease association.

Onset of fractures is in infancy.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2095 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2095 SERPINF1 Zornitza Stark Classified gene: SERPINF1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2095 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2094 SERPINF1 Zornitza Stark gene: SERPINF1 was added
gene: SERPINF1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: SERPINF1.
Mode of inheritance for gene: SERPINF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERPINF1 were set to 28689307
Phenotypes for gene: SERPINF1 were set to Osteogenesis imperfecta, type VI, MIM# 613982
Review for gene: SERPINF1 was set to GREEN
Added comment: Established gene-disease association.

Onset of fractures is in infancy.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2093 PPIB Zornitza Stark Gene: ppib has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2093 PPIB Zornitza Stark gene: PPIB was added
gene: PPIB was added to Baby Screen+ newborn screening. Sources: Expert list
skeletal tags were added to gene: PPIB.
Mode of inheritance for gene: PPIB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIB were set to 19781681; 32392875
Phenotypes for gene: PPIB were set to Osteogenesis imperfecta, type IX, MIM# 259440
Review for gene: PPIB was set to RED
Added comment: Established gene-diseases association.

Most reported families have had severe OI, presenting perinatally, therefore exclude.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2092 PLOD2 Zornitza Stark Gene: plod2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2091 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2091 P3H1 Zornitza Stark Classified gene: P3H1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2091 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2090 P3H1 Zornitza Stark gene: P3H1 was added
gene: P3H1 was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, skeletal tags were added to gene: P3H1.
Mode of inheritance for gene: P3H1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: P3H1 were set to 17277775; 18566967
Phenotypes for gene: P3H1 were set to Osteogenesis imperfecta, type VIII, (MIM# 610915)
Review for gene: P3H1 was set to GREEN
Added comment: More than 15 families reported.

Congenital onset.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2089 MESD Zornitza Stark Gene: mesd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2089 MESD Zornitza Stark Classified gene: MESD as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2089 MESD Zornitza Stark Gene: mesd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2088 MESD Zornitza Stark gene: MESD was added
gene: MESD was added to Baby Screen+ newborn screening. Sources: Expert Review
treatable, skeletal tags were added to gene: MESD.
Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MESD were set to 31564437; 35092157; 33596325; 31564437
Phenotypes for gene: MESD were set to Osteogenesis imperfecta, type XX, MIM# 618644
Review for gene: MESD was set to GREEN
Added comment: More than 5 families reported.

Severe form of OI, some perinatal lethal.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.2087 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2087 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2087 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2086 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, skeletal tags were added to gene: KDELR2.
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KDELR2 were set to Osteogenesis imperfecta 21, MIM# 619131
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.

Onset in infancy.

Improvement reported with bisphosphanates, similar to other OI.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2085 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2085 FKBP10 Zornitza Stark Classified gene: FKBP10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2085 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2084 FKBP10 Zornitza Stark gene: FKBP10 was added
gene: FKBP10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: FKBP10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKBP10 were set to 34173012
Phenotypes for gene: FKBP10 were set to Osteogenesis imperfecta, type XI, OMIM:610968
Review for gene: FKBP10 was set to GREEN
Added comment: Well established gene-disease association.

Early-onset bone fractures and progressive skeletal deformities.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2083 BMP1 Zornitza Stark Gene: bmp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2083 BMP1 Zornitza Stark Classified gene: BMP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2083 BMP1 Zornitza Stark Gene: bmp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2082 BMP1 Zornitza Stark gene: BMP1 was added
gene: BMP1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: BMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP1 were set to 33818922
Phenotypes for gene: BMP1 were set to Osteogenesis imperfecta, type XIII , MIM#614856
Review for gene: BMP1 was set to GREEN
Added comment: Rare cause of OI. 20 families reported.

Treatment: bisphosphanates.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2081 SARS Zornitza Stark Classified gene: SARS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2081 SARS Zornitza Stark Gene: sars has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2080 SCARB2 Zornitza Stark Classified gene: SCARB2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2080 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2079 SERPING1 Zornitza Stark Gene: serping1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2079 SERPING1 Zornitza Stark Classified gene: SERPING1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2079 SERPING1 Zornitza Stark Gene: serping1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2078 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2078 SGPL1 Zornitza Stark Classified gene: SGPL1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2078 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2077 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2077 SLC1A3 Zornitza Stark Classified gene: SLC1A3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2077 SLC1A3 Zornitza Stark Gene: slc1a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2076 SMARCD2 Zornitza Stark Classified gene: SMARCD2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2076 SMARCD2 Zornitza Stark Gene: smarcd2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2075 SNX10 Zornitza Stark Gene: snx10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2075 SNX10 Zornitza Stark Classified gene: SNX10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2075 SNX10 Zornitza Stark Gene: snx10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2074 SORD Zornitza Stark Gene: sord has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2074 SORD Zornitza Stark Classified gene: SORD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2074 SORD Zornitza Stark Gene: sord has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2073 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2073 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2073 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2072 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2071 STAT1 Zornitza Stark Classified gene: STAT1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2071 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2070 STAT1 Zornitza Stark reviewed gene: STAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.2070 STIM1 Zornitza Stark Gene: stim1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2070 STIM1 Zornitza Stark Classified gene: STIM1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2070 STIM1 Zornitza Stark Gene: stim1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2069 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2069 STK4 Zornitza Stark Classified gene: STK4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2069 STK4 Zornitza Stark Gene: stk4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2068 STX16 Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2068 STX16 Zornitza Stark Classified gene: STX16 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2068 STX16 Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2067 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2066 SYT2 Zornitza Stark Classified gene: SYT2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2066 SYT2 Zornitza Stark Gene: syt2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2065 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2065 TBL1X Zornitza Stark Classified gene: TBL1X as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2065 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2064 TF Zornitza Stark Gene: tf has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2064 TF Zornitza Stark Classified gene: TF as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2064 TF Zornitza Stark Gene: tf has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2063 SCARB2 Lilian Downie gene: SCARB2 was added
gene: SCARB2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SCARB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCARB2 were set to PMID: 34337151, PMID: 35346091, PMID: 26677510
Phenotypes for gene: SCARB2 were set to Epilepsy, progressive myoclonic 4, with or without renal failure MIM#254900
Review for gene: SCARB2 was set to RED
Added comment: Onset not <5
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SGPL1 Lilian Downie gene: SGPL1 was added
gene: SGPL1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to PMID: 28165343
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 MIM#617575
Review for gene: SGPL1 was set to RED
Added comment: infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS), resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects

Rx Hydrocortisone, kidney transplant (treatment doesn't fit screening model as would need to have ESRD before you had it?)
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SLC1A3 Lilian Downie gene: SLC1A3 was added
gene: SLC1A3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SLC1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A3 were set to PMID: 32754645
Phenotypes for gene: SLC1A3 were set to Episodic ataxia, type 6 MIM#612656
Review for gene: SLC1A3 was set to RED
Added comment: ataxia occurs with febrile illnesses
Episodic attacks lasted 2 to 3 hours and were often associated with nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, and/or slurred speech
Not consistently in children <5 and variable severity

Suggested Rx acetazolamide
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SMARCD2 Lilian Downie gene: SMARCD2 was added
gene: SMARCD2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMARCD2 were set to PubMed: 28369036, 33279574, 33025377
Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2 MIM#617475
Review for gene: SMARCD2 was set to GREEN
Added comment: recurrent infections due to defective neutrophil development. Bone marrow findings include paucity of neutrophil granulocytes, absence of granule proteins in neutrophils, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and patients may die in early childhood unless they undergo hematopoietic stem cell transplantation. Most patients have additional findings, including delayed development, mild dysmorphic features, tooth abnormalities, and distal skeletal defects

Rx bone marrow transplant
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SNX10 Lilian Downie gene: SNX10 was added
gene: SNX10 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SNX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNX10 were set to PMID: 30885997, PMID: 22499339
Phenotypes for gene: SNX10 were set to Osteopetrosis, autosomal recessive 8 MIM#615085
Review for gene: SNX10 was set to GREEN
Added comment: macrocephaly
failure to thrive
osteopetrosis

Rx bone marrow tranplant
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SORD Lilian Downie gene: SORD was added
gene: SORD was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SORD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SORD were set to PMID: 32367058
Phenotypes for gene: SORD were set to Sorbitol dehydrogenase deficiency with peripheral neuropathy MIM#618912
Review for gene: SORD was set to RED
Added comment: Slowly progressive, onset not consistently <5

Rx epalrestat and ranirestat
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SOX3 Lilian Downie gene: SOX3 was added
gene: SOX3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SOX3 were set to PMID: 31678974, PMID: 15800844
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked MIM#312000
Review for gene: SOX3 was set to AMBER
Added comment: Amber in our mendeliome - reviewed for ID
Green in pituitary disorders

Xq27.1 duplication most common mechanism - inclusion might be a question of whether we can detect CNV's in this region

neonatal hypoglycemia and growth hormone deficiency in addition to variable deficiencies of other pituitary hormones. Brain hypoplasia of the anterior pituitary with hypoplasia or absence of the lower half of the infundibulum

Rx Growth hormone, levothyroxine, hydrocortisone
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 STAT1 Lilian Downie gene: STAT1 was added
gene: STAT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STAT1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STAT1 were set to PMID: 31512162, PMID: 27117246
Phenotypes for gene: STAT1 were set to Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive MIM#613796
Review for gene: STAT1 was set to GREEN
Added comment: combined immunodeficiency
autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function.
gain of function mutations - treat rituxomab
complete - treat BMT
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 STIM1 Lilian Downie gene: STIM1 was added
gene: STIM1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STIM1 were set to PMID: 26469693, PMID: 30949876, PMID: 26560041
Phenotypes for gene: STIM1 were set to Immunodeficiency 10 MIM612783
Review for gene: STIM1 was set to GREEN
Added comment: recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta

Rx bone marrow transpant

Age of onset is consistently <5 but the severity of infections is highly variable - treatment if the phenotype is severe
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 STK4 Lilian Downie gene: STK4 was added
gene: STK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK4 were set to PMID: 22294732
Phenotypes for gene: STK4 were set to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM#614868
Review for gene: STK4 was set to GREEN
Added comment: primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect

Rx bone marrow transplant
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 STX16 Lilian Downie gene: STX16 was added
gene: STX16 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: STX16 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: STX16 were set to PMID: 33247854, PMID: 34477200, PMID: 29072892
Phenotypes for gene: STX16 were set to Pseudohypoparathyroidism, type IB MIM#603233
Review for gene: STX16 was set to GREEN
Added comment: characterized clinically by isolated renal PTH resistance manifest as hypocalcemia, hyperphosphatemia, and increased serum PTH
without other features of Albright hereditary osteodystrophy
Rx Calcium, calcitriol, levothyroxine, growth hormone
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SYT2 Lilian Downie gene: SYT2 was added
gene: SYT2 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SYT2 were set to PMID: 32250532, 32776697
Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461
Review for gene: SYT2 was set to GREEN
Added comment: Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.

Only report biallelic for newborn screening ?
monoallelic causes a later onset distal weakness/neuropathy phenotype - still childhood but variable or not clear - not consistently <5yrs
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 TF Lilian Downie gene: TF was added
gene: TF was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TF were set to PMID: 32028041, PMID: 19579082, PMID: 11110675
Phenotypes for gene: TF were set to Atransferrinemia MIM#209300
Review for gene: TF was set to GREEN
Added comment: Hypochromic microcytic anaemia from absent transferrin - presents in infancy


Rx Red cell transfusions, deferoxamine
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2063 SAR1B Zornitza Stark Classified gene: SAR1B as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2063 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2062 SAR1B Zornitza Stark gene: SAR1B was added
gene: SAR1B was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, gastrointestinal tags were added to gene: SAR1B.
Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SAR1B were set to Chylomicron retention disease, MIM# 246700
Review for gene: SAR1B was set to GREEN
Added comment: Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. Well established gene-disease association.

Congenital onset.

Treatment: low-fat diet with supplementation of fat-soluble vitamins (A, D, E, and K) and oral essential fatty acid supplementation

Non-genetic confirmatory testing: total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2061 SAMD9L Zornitza Stark Gene: samd9l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2061 SAMD9L Zornitza Stark Classified gene: SAMD9L as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2061 SAMD9L Zornitza Stark Gene: samd9l has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2060 SAMD9L Zornitza Stark gene: SAMD9L was added
gene: SAMD9L was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: SAMD9L.
Mode of inheritance for gene: SAMD9L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9L were set to 31306780
Phenotypes for gene: SAMD9L were set to Ataxia-pancytopenia syndrome, MIM# 159550
Review for gene: SAMD9L was set to GREEN
Added comment: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML).

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2059 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2059 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2059 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2058 SAMD9 Zornitza Stark gene: SAMD9 was added
gene: SAMD9 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SAMD9 were set to 31306780
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome, MIM# 617053
Review for gene: SAMD9 was set to GREEN
Added comment: MIRAGE syndrome (MIRAGE) is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. The condition is often fatal within the first decade of life, usually as a result of invasive infection.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2057 THAP11 Zornitza Stark Gene: thap11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2056 THAP11 Zornitza Stark Classified gene: THAP11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2056 THAP11 Zornitza Stark Gene: thap11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2055 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2055 TMEM165 Zornitza Stark Classified gene: TMEM165 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2055 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2054 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2054 TNFRSF13B Zornitza Stark Classified gene: TNFRSF13B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2054 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2053 TNFAIP3 Zornitza Stark Gene: tnfaip3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2053 TNFAIP3 Zornitza Stark Classified gene: TNFAIP3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2053 TNFAIP3 Zornitza Stark Gene: tnfaip3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2052 THAP11 Lilian Downie gene: THAP11 was added
gene: THAP11 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: THAP11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THAP11 were set to PMID: 28449119, PMID: 31905202
Phenotypes for gene: THAP11 were set to Combined methylmalonic acidemia and homocystinuria, cblX like 2
Review for gene: THAP11 was set to RED
Added comment: Single patient?
Not in our mendeliome
Not enough gene disease validity
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2052 TMEM165 Lilian Downie gene: TMEM165 was added
gene: TMEM165 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM165 were set to PMID: 28323990, PMID: 35693943, PMID: 22683087
Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk MIM#614727
Review for gene: TMEM165 was set to AMBER
Added comment: Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern

Rx D-galactose (single paper, 2 unrelated patients and an in vitro study) ?inadequete evidence for treatment? Might need to check with JC if we would offer it maybe include
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2052 TNFAIP3 Lilian Downie gene: TNFAIP3 was added
gene: TNFAIP3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFAIP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFAIP3 were set to PMID: 31587140, PMID: 33101300
Phenotypes for gene: TNFAIP3 were set to Autoinflammatory syndrome, familial, Behcet-like 1 MIM#616744
Review for gene: TNFAIP3 was set to RED
Added comment: Average age of onset 5yrs - too variable re age of onset.

painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells.

Treatment: Colchicine, glucocorticoid, mesalazine, cyclosporine, methotrexate, azathioprine, anakinra, rituximab, tocilizumab, infliximab
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2052 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2052 RNPC3 Zornitza Stark Classified gene: RNPC3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2052 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2050 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2050 RASGRP1 Zornitza Stark Classified gene: RASGRP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2050 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2049 RASGRP1 Zornitza Stark gene: RASGRP1 was added
gene: RASGRP1 was added to Baby Screen+ newborn screening. Sources: Literature
treatable, immunological tags were added to gene: RASGRP1.
Mode of inheritance for gene: RASGRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RASGRP1 were set to Immunodeficiency 64 (MIM#618534)
Review for gene: RASGRP1 was set to GREEN
Added comment: Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity.

Severe disorder, fatal outcomes reported in childhood.

Treatment: BMT.

Non-genetic confirmatory testing: no.
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.2048 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2047 RAC2 Zornitza Stark Classified gene: RAC2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2047 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2045 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2045 PLS3 Zornitza Stark Classified gene: PLS3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2045 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2044 PLS3 Zornitza Stark gene: PLS3 was added
gene: PLS3 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLS3 were set to 32655496; 25209159; 29736964; 29884797; 28777485; 24088043
Phenotypes for gene: PLS3 were set to Bone mineral density QTL18, osteoporosis - MIM#300910
Review for gene: PLS3 was set to GREEN
Added comment: Females mildly affected: exclude from screening.

Presentation in males similar to OI, though also variable in severity.

Treatment: safe handling techniques, bisphosphonates, pamidronate, zoledronic acid, teriparatide, denosumab, alendronate

Non-genetic confirmatory testing: skeletal survey
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2043 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2043 OTULIN Zornitza Stark Classified gene: OTULIN as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2043 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2042 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OTULIN.
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
Added comment: Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection.

Onset is generally in infancy.

Treatment: inflixiimab, anakinra, etanercept, corticosteroids.

Non-genetic confirmatory testing: no.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2041 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2041 OAS1 Zornitza Stark Classified gene: OAS1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2041 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2040 OAS1 Zornitza Stark gene: OAS1 was added
gene: OAS1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: OAS1.
Mode of inheritance for gene: OAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OAS1 were set to 34145065; 29455859
Phenotypes for gene: OAS1 were set to Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinaemia, MIM#618042
Review for gene: OAS1 was set to GREEN
Added comment: Immunodeficiency-100 with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) is primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis (PAP) in the first months of life. Affected individuals may have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood.

Treatment: IVIG; BMT is curative.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2039 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2039 NFKBIA Zornitza Stark Classified gene: NFKBIA as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2039 NFKBIA Zornitza Stark Gene: nfkbia has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2038 NFKBIA Zornitza Stark gene: NFKBIA was added
gene: NFKBIA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: NFKBIA.
Mode of inheritance for gene: NFKBIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NFKBIA were set to Ectodermal dysplasia and immunodeficiency 2 MIM# 612132
Review for gene: NFKBIA was set to GREEN
Added comment: 12 heterozygous variants were identified in 15 unrelated individuals (de novo in 14 individuals and somatic mosaicism in 1 individual).

Functional studies & two mouse models; demonstrate reported NFKBIA gain-of-function variants resulting in impaired NFKB1 activity.

The majority of individuals displayed recurrent infections, chronic diarrhoea, agammaglobulinaemia, increased IgM, and defects in teeth (hair, nail, sweat glands).

Onset is generally in infancy.

Treatment: BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2037 NAXE Zornitza Stark Gene: naxe has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2037 NAXE Zornitza Stark gene: NAXE was added
gene: NAXE was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXE.
Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXE were set to 27122014; 27616477; 31758406
Phenotypes for gene: NAXE were set to Encephalopathy, progressive, early-onset, with brain oedema and/or leukoencephalopathy, MIM# 617186
Review for gene: NAXE was set to RED
Added comment: Early-onset progressive encephalopathy with brain oedema and/or leukoencephalopathy-1 (PEBEL1) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions. More than 5 unrelated families reported.

Treatment: niacin

However, single case reported. Treatment not established.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2036 NAXD Zornitza Stark Gene: naxd has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2036 NAXD Zornitza Stark Classified gene: NAXD as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.2036 NAXD Zornitza Stark Gene: naxd has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.2035 NAXD Zornitza Stark gene: NAXD was added
gene: NAXD was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: NAXD.
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410; 31755961; 32462209; 35231119
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 MIM#618321
Review for gene: NAXD was set to AMBER
Added comment: Seven unrelated cases, episodes of fever/infection prior to deterioration reported. Variable phenotype: one patient reported with neurodevelopmental disorder, autism spectrum disorder and a muscular-dystrophy-like myopathy; another with progressive encephalopathy with brain oedema. Patient cells and muscle biopsies also showed impaired mitochondrial function, higher sensitivity to metabolic stress, and decreased mitochondrial reactive oxygen species production. In vitro functional assays also conducted.

Treatment: niacin

However, only two cases reported. Treatment not established.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2034 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2034 MYD88 Zornitza Stark Classified gene: MYD88 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2034 MYD88 Zornitza Stark Gene: myd88 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2033 MYD88 Zornitza Stark gene: MYD88 was added
gene: MYD88 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MYD88.
Mode of inheritance for gene: MYD88 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYD88 were set to 18669862; 20538326; 31301515
Phenotypes for gene: MYD88 were set to Immunodeficiency 68, MIM# 612260
Review for gene: MYD88 was set to GREEN
Added comment: Immunodeficiency-68 (IMD68) is an autosomal recessive primary immunodeficiency characterized by severe systemic and invasive bacterial infections beginning in infancy or early childhood. The most common organisms implicated are Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas, although other organisms may be observed.

At least 7 families and a mouse model.

Treatment: Prophylactic antibiotic treatment, pneumococcal, meningococcal, haemophilus influenzae vaccines, and immunoglobulin replacement.

Non-genetic confirmatory testing: toll-like receptor function
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2032 MTHFS Zornitza Stark Gene: mthfs has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2032 MTHFS Zornitza Stark gene: MTHFS was added
gene: MTHFS was added to Baby Screen+ newborn screening. Sources: Expert list
metabolic tags were added to gene: MTHFS.
Mode of inheritance for gene: MTHFS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFS were set to 30031689; 31844630; 22303332
Phenotypes for gene: MTHFS were set to Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination, 618367
Review for gene: MTHFS was set to RED
Added comment: Established gene-disease association.

Onset in infancy. Severe disorder.

Treatment: single report of some improvement with combination of oral L-5- methyltetrahydrofolate and intramuscular methylcobalamin
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2031 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2031 MTHFD1 Zornitza Stark Classified gene: MTHFD1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2031 MTHFD1 Zornitza Stark Gene: mthfd1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2030 MTHFD1 Zornitza Stark gene: MTHFD1 was added
gene: MTHFD1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological, haematological tags were added to gene: MTHFD1.
Mode of inheritance for gene: MTHFD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTHFD1 were set to 32414565; 19033438
Phenotypes for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780
Review for gene: MTHFD1 was set to GREEN
Added comment: 8 individuals from 4 unrelated families have been reported; multiple mouse models

7 individuals were Compound heterozygous (nonsense & missense) and 1 was homozygous (missense) for MTHFD1 variants often resulting in alteration of highly conserved residues in binding-sites.

Individuals typically present with megaloblastic anaemia, atypical hemolytic uremic syndrome, hyperhomocysteinaemia, microangiopathy, recurrent infections and autoimmune diseases.

Treatment: hydroxocobalamin, folinic acid and betaine

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, complete blood count with MCV, plasma homocysteine and methylmalonic acid levels, CSF
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2029 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2029 MNX1 Zornitza Stark Classified gene: MNX1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2029 MNX1 Zornitza Stark Gene: mnx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2027 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2027 MALT1 Zornitza Stark Classified gene: MALT1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2027 MALT1 Zornitza Stark Gene: malt1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2026 MALT1 Zornitza Stark gene: MALT1 was added
gene: MALT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MALT1.
Mode of inheritance for gene: MALT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MALT1 were set to Immunodeficiency 12 MIM# 615468
Review for gene: MALT1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency.

Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains.

All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.

Treatment: prophylactic antibiotics, IVIG, BMT.

Non-genetic confirmatory testing: no
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2025 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2025 MAGT1 Zornitza Stark Classified gene: MAGT1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2025 MAGT1 Zornitza Stark Gene: magt1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2024 MAGT1 Zornitza Stark gene: MAGT1 was added
gene: MAGT1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: MAGT1.
Mode of inheritance for gene: MAGT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MAGT1 were set to 31036665; 31714901
Phenotypes for gene: MAGT1 were set to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia (MIM# 300853)
Review for gene: MAGT1 was set to GREEN
Added comment: XMEN is an X-linked recessive immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. Affected individuals have chronic Epstein-Barr virus (EBV) infection and are susceptible to the development of EBV-associated B-cell lymphoproliferative disorders.

Variable age of onset, including in early childhood.

Treatment: Mg supplementation; IVIG, BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile, Carbohydrate deficient glycosylation profile
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2023 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2023 LRBA Zornitza Stark Classified gene: LRBA as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2023 LRBA Zornitza Stark Gene: lrba has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2021 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2021 LIG1 Zornitza Stark Classified gene: LIG1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2021 LIG1 Zornitza Stark Gene: lig1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2019 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2019 LEP Zornitza Stark Classified gene: LEP as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2019 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2018 LEP Zornitza Stark gene: LEP was added
gene: LEP was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: LEP.
Mode of inheritance for gene: LEP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LEP were set to 26567097
Phenotypes for gene: LEP were set to Obesity, morbid, due to leptin deficiency (MIM#614962)
Review for gene: LEP was set to GREEN
Added comment: Established gene-disease association.

Onset is in infancy/early childhood. Similar disorders included.

Treatment: metreleptin.

Non-genetic confirmatory testing: leptin level.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2017 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2017 JAGN1 Zornitza Stark Classified gene: JAGN1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2017 JAGN1 Zornitza Stark Gene: jagn1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2016 JAGN1 Zornitza Stark gene: JAGN1 was added
gene: JAGN1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: JAGN1.
Mode of inheritance for gene: JAGN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAGN1 were set to 25129144
Phenotypes for gene: JAGN1 were set to Neutropenia, severe congenital, 6, autosomal recessive, MIM# 616022
Review for gene: JAGN1 was set to GREEN
Added comment: Established gene-disease association.

Typically presents in early childhood with severe infections.

Treatment: G-CSF, BMT.

Non-genetic confirmatory testing: complete blood count, bone marrow aspiration and biopsy
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2015 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2015 TNFRSF13C Zornitza Stark Classified gene: TNFRSF13C as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.2015 TNFRSF13C Zornitza Stark Gene: tnfrsf13c has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.2014 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2014 ITK Zornitza Stark Classified gene: ITK as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2014 ITK Zornitza Stark Gene: itk has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2013 ITK Zornitza Stark gene: ITK was added
gene: ITK was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: ITK.
Mode of inheritance for gene: ITK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITK were set to Lymphoproliferative syndrome 1, MIM# 613011
Review for gene: ITK was set to GREEN
Added comment: 7 individuals from 5 unrelated families reported homozygous (missense/ nonsense) ITK variants consistent with Lymphoproliferative syndrome phenotype. Triggered by EBV infection.

Two ITK-deficient mouse models demonstrated reduced T cells (CD4+), causing decreased CD4 to CD8 ratio.

Patients displayed early onset of features typically including fever, lymphadenopathy, autoimmune disorders, low immunoglobulins and high EBV viral load.

Fatal without BMT.

Non-genetic confirmatory testing: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2012 IRS4 Zornitza Stark Gene: irs4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2012 IRS4 Zornitza Stark Classified gene: IRS4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2012 IRS4 Zornitza Stark Gene: irs4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2010 IL36RN Zornitza Stark Gene: il36rn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2010 IL36RN Zornitza Stark Classified gene: IL36RN as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2010 IL36RN Zornitza Stark Gene: il36rn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2009 IL36RN Zornitza Stark gene: IL36RN was added
gene: IL36RN was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL36RN.
Mode of inheritance for gene: IL36RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL36RN were set to 31286990
Phenotypes for gene: IL36RN were set to Psoriasis 14, pustular, MIM# 614204
Review for gene: IL36RN was set to GREEN
Added comment: Generalized pustular psoriasis (GPP) is a life-threatening disease characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein.

Variable age of onset but predominantly in infancy/early childhood.

Treatment: ustekinumab, secukinumab, etanercept.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2008 IL2RA Zornitza Stark Gene: il2ra has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2008 IL2RA Zornitza Stark Classified gene: IL2RA as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2008 IL2RA Zornitza Stark Gene: il2ra has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2007 IL2RA Zornitza Stark gene: IL2RA was added
gene: IL2RA was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL2RA.
Mode of inheritance for gene: IL2RA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL2RA were set to Immunodeficiency 41 with lymphoproliferation and autoimmunity, MIM# 606367
Review for gene: IL2RA was set to GREEN
Added comment: Immunodeficiency-41 is a disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation.

At least 4 unrelated families reported.

Treatment: rapamycin, bone marrow transplant.

Confirmatory non-genetic testing: flow cytometric analysis.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2006 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2006 IL21R Zornitza Stark Classified gene: IL21R as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2006 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2005 IL21R Zornitza Stark gene: IL21R was added
gene: IL21R was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IL21R.
Mode of inheritance for gene: IL21R was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IL21R were set to Immunodeficiency 56, MIM# 615207
Review for gene: IL21R was set to GREEN
Added comment: Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections.

More than 20 individuals reported. Recent series of 13 individuals: the main clinical manifestations were recurrent bacterial (84.6%), fungal (46.2%), and viral (38.5%) infections; cryptosporidiosis-associated cholangitis (46.2%); and asthma (23.1%). Inflammatory skin diseases (15.3%) and recurrent anaphylaxis (7.9%) constitute novel phenotypes of this combined immunodeficiency. Most patients exhibited hypogammaglobulinaemia and reduced proportions of memory B cells, circulating T follicular helper cells, MAIT cells and terminally differentiated NK cells. However, IgE levels were elevated in 50% of IL-21R-deficient patients.

Onset: infancy/early childhood.

Treatment: BMT.

Non-genetic confirmatory testing: immunoglobulin levels.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2004 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2004 IL1RN Zornitza Stark Classified gene: IL1RN as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2004 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2002 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2002 IKZF1 Zornitza Stark Classified gene: IKZF1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2002 IKZF1 Zornitza Stark Gene: ikzf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2001 IKZF1 Zornitza Stark gene: IKZF1 was added
gene: IKZF1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IKZF1 were set to Immunodeficiency, common variable, 13 MIM# 616873
Added comment: Over 25 individuals from 9 unrelated families with variants in IKZF1 displaying Immunodeficiency; three mouse models Heterozygous missense, frameshift and deletion variants in IKZF1 gene resulting in loss or alteration of a zinc finger DNA contact site cause LoF. Typically presents with recurrent bacterial respiratory infections, hypogammaglobulinaemia and low Ig levels; variable age of onset.

PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.

Included primarily for LoF phenotype.

Treatment: IVIG and BMT.

Non-genetic confirmatory testing: immunoglobulin levels
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.2000 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.2000 IKBKB Zornitza Stark Classified gene: IKBKB as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.2000 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1998 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1998 IFNGR2 Zornitza Stark Classified gene: IFNGR2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1998 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1997 IFNGR2 Zornitza Stark gene: IFNGR2 was added
gene: IFNGR2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: IFNGR2.
Mode of inheritance for gene: IFNGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR2 were set to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Review for gene: IFNGR2 was set to AMBER
Added comment: At least 5 unrelated families reported.

Commonest trigger is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1996 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1996 IFNGR1 Zornitza Stark Classified gene: IFNGR1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1996 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1995 IFNGR1 Zornitza Stark gene: IFNGR1 was added
gene: IFNGR1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: IFNGR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: IFNGR1 were set to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Review for gene: IFNGR1 was set to AMBER
Added comment: Variable age of onset. Most common precipitant is BCG vaccination, which is not part of the routine schedule in Australia, therefore exclude.

Treatment: BMT; avoidance of BCG.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1994 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1994 IFITM5 Zornitza Stark Classified gene: IFITM5 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1994 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1993 IFITM5 Zornitza Stark gene: IFITM5 was added
gene: IFITM5 was added to Baby Screen+ newborn screening. Sources: Expert list
5'UTR, treatable, skeletal tags were added to gene: IFITM5.
Mode of inheritance for gene: IFITM5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFITM5 were set to 22863190; 22863195; 32383316; 24519609
Phenotypes for gene: IFITM5 were set to Osteogenesis imperfecta, type V MIM#610967
Review for gene: IFITM5 was set to GREEN
Added comment: A recurrent c.-14C>T variant has been reported in many patients with type V OI. It introduces an alternative in-frame start codon upstream that is stronger than the reference start codon in transfected HEK cells (PMIDs: 22863190, 22863195). However, the effect of mutant protein (5 amino acids longer) remains unknown but neomorphic mechanism is a widely accepted hypothesis (PMIDs: 25251575, 32383316).

Variable severity, including within families. However, severe perinatal presentations reported.

Treatment: bisphosphanates.

Non-genetic confirmatory testing: skeletal survey.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1992 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1992 ICOS Zornitza Stark Classified gene: ICOS as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1992 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1990 IARS Zornitza Stark Classified gene: IARS as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1990 IARS Zornitza Stark Gene: iars has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1988 TNFRSF1A Zornitza Stark Gene: tnfrsf1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1988 TNFRSF1A Zornitza Stark Classified gene: TNFRSF1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1988 TNFRSF1A Zornitza Stark Gene: tnfrsf1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1987 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1987 TOP2B Zornitza Stark Classified gene: TOP2B as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1987 TOP2B Zornitza Stark Gene: top2b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1986 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1986 TPK1 Zornitza Stark Classified gene: TPK1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1986 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1985 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1985 TRNT1 Zornitza Stark Classified gene: TRNT1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1985 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1984 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1984 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1984 TRPM6 Zornitza Stark Classified gene: TRPM6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1984 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1983 UCP2 Zornitza Stark Gene: ucp2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1982 TNFRSF1A Lilian Downie gene: TNFRSF1A was added
gene: TNFRSF1A was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TNFRSF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNFRSF1A were set to PMID: 11175303, PMID: 32066461, PMID: 29773275, PMID: 32831641
Phenotypes for gene: TNFRSF1A were set to Periodic fever, familial MIM#142680
Penetrance for gene: TNFRSF1A were set to Incomplete
Review for gene: TNFRSF1A was set to RED
Added comment: Strong gene disease association
Childhood onset but age not consistently under 5 and cases of adult onset
reports of variable penetrance
Rx
NSAIDs, corticosteroids, Etanercept , anakinra, canakinumab, tocilizumab

because there is no non-molecular confirmatory test I think should be red for variability of age of onset and severity of symptoms.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1982 TPK1 Lilian Downie gene: TPK1 was added
gene: TPK1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPK1 were set to PMID: 33086386, 32679198, 22152682, PMID: 33231275
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) MIM#614458
Review for gene: TPK1 was set to GREEN
Added comment: Strong gene disease association
Variable age of onset but always under 5years

Thiamine metabolism dysfunction syndrome-5 (THMD5) is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (Mayr et al., 2011).

Biotin and thiamine therapy - newer evidence (2021) suggests early thiamine therapy may prevent any neurologic deficits.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1982 TRNT1 Lilian Downie gene: TRNT1 was added
gene: TRNT1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRNT1 were set to PMID: 25193871, PMID: 23553769, PMID: 33936027, PMID: 26494905
Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay MIM#616084
Review for gene: TRNT1 was set to AMBER
Added comment: Onset infancy
Strong gene disease association

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013).

Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment

Allelic disease: Retinitis pigmentosa and erythrocytic microcytosis MIM#616959. Also AR.
DeLuca et al. (2016) concluded that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina - this has teenage onset and is not treatable. can we exclude these variants?
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1982 TRPM6 Lilian Downie gene: TRPM6 was added
gene: TRPM6 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to PMID: 35903165, PMID: 18818955
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal MIM#602014
Review for gene: TRPM6 was set to GREEN
Added comment: Hypomagnaesemia and hypocalcaemia
Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009).
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1982 UNG Zornitza Stark Gene: ung has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1982 UNG Zornitza Stark Classified gene: UNG as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1982 UNG Zornitza Stark Gene: ung has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1981 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1981 UMPS Zornitza Stark Classified gene: UMPS as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1981 UMPS Zornitza Stark Gene: umps has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1980 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1978 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1978 HSD11B2 Zornitza Stark Classified gene: HSD11B2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1978 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1977 HSD11B2 Zornitza Stark gene: HSD11B2 was added
gene: HSD11B2 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, endocrine tags were added to gene: HSD11B2.
Mode of inheritance for gene: HSD11B2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HSD11B2 were set to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025
Review for gene: HSD11B2 was set to GREEN
Added comment: Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone. More than 10 unrelated families reported.

Onset is usually in infancy or early childhood.

Non-genetic confirmatory testing: aldosterone, renin, potassium levels
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1976 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1976 HOGA1 Zornitza Stark Classified gene: HOGA1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1976 HOGA1 Zornitza Stark Gene: hoga1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1975 HOGA1 Zornitza Stark gene: HOGA1 was added
gene: HOGA1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: HOGA1.
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 20797690; 21896830; 22391140
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III MIM#613616
Review for gene: HOGA1 was set to GREEN
Added comment: Well-established association with primary hyperoxaluria type III. c.700+5G>T is a recurrent pathogenic variant in European populations (possibly founder) and has high frequency in gnomad (0.2-0.3%).

Onset in infancy, progressive multi-system disorder.

Treatment: pyridoxine, drinking large volumes, alkalinzation of urine, pyrophosphate-containing solutions, liver-kidney transplant

Non-genetic confirmatory testing: urinary oxalate
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1974 UMPS Lilian Downie changed review comment from: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list; to: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Better check with John who wrote the paper!! PMID: 25030255

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1974 UMPS Lilian Downie gene: UMPS was added
gene: UMPS was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UMPS were set to PMID: 9042911, PMID: 28205048, PMID: 25757096, PMID: 33489760
Phenotypes for gene: UMPS were set to Orotic aciduria MIM#258900
Review for gene: UMPS was set to GREEN
Added comment: megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001).

Treat uridine
Very rare only 20 cases but treatable.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1974 UNG Lilian Downie gene: UNG was added
gene: UNG was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: UNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNG were set to PubMed: 12958596, PMID: 15967827, PMID: 19202054, PMID: 16860315
Phenotypes for gene: UNG were set to Immunodeficiency with hyper IgM, type 5 MIM#608106
Review for gene: UNG was set to RED
Added comment: normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations.
susceptibility to bacterial infections, lymphoid hyperplasia
only 3 patients reported in a single paper ?
Rx immunoglobulin replacement according to Rx genes but I can't find actual papers - i don't think there is enough evidence regarding age of onset or treatability.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1974 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1974 HELLS Zornitza Stark Classified gene: HELLS as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1974 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1972 USP18 Zornitza Stark Gene: usp18 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1972 USP18 Zornitza Stark Classified gene: USP18 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1972 USP18 Zornitza Stark Gene: usp18 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1971 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1970 VKORC1 Zornitza Stark Classified gene: VKORC1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1970 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1969 WDR1 Zornitza Stark Gene: wdr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1969 WDR1 Zornitza Stark Classified gene: WDR1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1969 WDR1 Zornitza Stark Gene: wdr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1968 GPIHBP1 Zornitza Stark Gene: gpihbp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1968 GPIHBP1 Zornitza Stark Classified gene: GPIHBP1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1968 GPIHBP1 Zornitza Stark Gene: gpihbp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1966 GHRHR Zornitza Stark Gene: ghrhr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1966 GHRHR Zornitza Stark Classified gene: GHRHR as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1966 GHRHR Zornitza Stark Gene: ghrhr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1964 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1964 GHR Zornitza Stark Classified gene: GHR as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1964 GHR Zornitza Stark Gene: ghr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1963 GHR Zornitza Stark gene: GHR was added
gene: GHR was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: GHR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GHR were set to Growth hormone insensitivity, partial, MIM# 604271; Laron dwarfism, MIM# 262500
Review for gene: GHR was set to GREEN
Added comment: Well established gene-disease association.

Congenital onset.

Treatment: growth hormone.

Non-genetic confirmatory testing: growth hormone stimulation test
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1962 GH1 Zornitza Stark Gene: gh1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1962 GH1 Zornitza Stark Classified gene: GH1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1962 GH1 Zornitza Stark Gene: gh1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1960 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1960 GFI1 Zornitza Stark Classified gene: GFI1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1960 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1958 USP18 Lilian Downie gene: USP18 was added
gene: USP18 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: USP18 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: USP18 were set to PMID: 31940699, 27325888, 12833411
Phenotypes for gene: USP18 were set to Pseudo-TORCH syndrome 2 MIM#617397
Review for gene: USP18 was set to AMBER
Added comment: antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. The disorder results from inappropriate activation of the interferon (IFN) immunologic pathway

Treatment Ruxolitinib (single patient only) - is a single patient with successful treatment enough?
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1958 VKORC1 Lilian Downie gene: VKORC1 was added
gene: VKORC1 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: VKORC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: VKORC1 were set to PMID:14765194, PMID: 26287237
Phenotypes for gene: VKORC1 were set to Vitamin K-dependent clotting factors, combined deficiency of, 2 MIM#607473
Review for gene: VKORC1 was set to AMBER
Added comment: Risk of intracranial haemmorhage in first weeks of life
Treatable with vitamin K
See below summary - feels like should be green for that homozygous mutation but not sure how to manage the gene overall? not report other variants?
Monoallelic - warfarin resistance

There is only one mutation known to result in the VKCFD2 phenotype. VKORC1:p.Arg98Trp causes diminished vitamin K epoxide reductase (VKOR) activity compared to that of the wild-type enzyme [15]. VKCFD2 patients exhibit severely diminished activities for the VKD coagulation factors and suffer spontaneous or surgery/injury induced bleeding episodes [16,17]. In addition to this haemorrhagic phenotype, abnormalities in epiphyseal growth have been reported in one case [18]. This phenotype is very rare. Worldwide, there are only four unrelated families known to be affected with VKCFD2 [16,17,18].
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1958 WDR72 Zornitza Stark Gene: wdr72 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1958 WDR72 Zornitza Stark Phenotypes for gene: WDR72 were changed from Distal renal tubular acidosis to Amelogenesis imperfecta, type IIA3, MIM# 613211; Distal RTA MONDO:0015827
Genomic newborn screening: BabyScreen+ v0.1957 WDR72 Zornitza Stark Classified gene: WDR72 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1957 WDR72 Zornitza Stark Gene: wdr72 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1956 WDR72 Zornitza Stark reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: None; Publications: 30028003; Phenotypes: Amelogenesis imperfecta, type IIA3, MIM# 613211, Distal RTA MONDO:0015827; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1956 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1956 WIPF1 Zornitza Stark Classified gene: WIPF1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1956 WIPF1 Zornitza Stark Gene: wipf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1955 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1955 WNK4 Zornitza Stark Classified gene: WNK4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1955 WNK4 Zornitza Stark Gene: wnk4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1954 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1954 ZBTB24 Zornitza Stark Classified gene: ZBTB24 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1954 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1953 ZNF143 Zornitza Stark Gene: znf143 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1953 ZNF143 Zornitza Stark Classified gene: ZNF143 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1953 ZNF143 Zornitza Stark Gene: znf143 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1952 WDR72 Lilian Downie gene: WDR72 was added
gene: WDR72 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR72 were set to PMID: 30028003, PMID: 30779877, PMID:36836560, PMID: 33033857
Phenotypes for gene: WDR72 were set to Distal renal tubular acidosis
Review for gene: WDR72 was set to GREEN
Added comment: Amelogenesis imperecta - thickened and disoloured dental enamal with RTA
Reduced penetrance or variable expression? Some patients only have the tooth phenotype...
Presents with polyuria and growth restriction
Treat with oral alkali replacement therapy, potassium chloride
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1952 WNK4 Lilian Downie gene: WNK4 was added
gene: WNK4 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: WNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WNK4 were set to PMID: 22073419, PMID: 31795491, PMID: 10869238,
Phenotypes for gene: WNK4 were set to Pseudohypoaldosteronism, type IIB MIM#614491
Review for gene: WNK4 was set to GREEN
Added comment: Hyperkalaemia and hypertension
Hypercalciuria
Hypocalcaemia
Decreased bone mineral density
Renal calcium stones
Treatable with thiazide diuretics
Variable age of onset from infancy to adulthood but highly effective treatment so leaning toward include.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1952 ZBTB24 Lilian Downie gene: ZBTB24 was added
gene: ZBTB24 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to PMID: 28128455, 21906047, 21596365, 23486536
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 MIM#614069
Review for gene: ZBTB24 was set to AMBER
Added comment: INfant onset
Agammaglobulinemia, facial anomalies, and mental retardation. Facial anomalies included broad, flat nasal bridge, hypertelorism, and epicanthal folds.
Treat immunoglobulin and bone marrow transplant however, this only treats the immune deficiency
Consider exclusion due to untreatable ID phenotype?
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1952 ZNF143 Lilian Downie gene: ZNF143 was added
gene: ZNF143 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: ZNF143 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF143 were set to PMID: 20301503, PMID: 27349184
Phenotypes for gene: ZNF143 were set to Combined methylmalonic acidemia and homocystinuria, cblX like 1
Review for gene: ZNF143 was set to RED
Added comment: Not in our mendeliome
Single case
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1952 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1952 FOLR1 Zornitza Stark Classified gene: FOLR1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1952 FOLR1 Zornitza Stark Gene: folr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1951 FOLR1 Zornitza Stark gene: FOLR1 was added
gene: FOLR1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, metabolic tags were added to gene: FOLR1.
Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOLR1 were set to 19732866; 30420205; 27743887
Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency, MIM# 613068
Review for gene: FOLR1 was set to GREEN
Added comment: Folate is a neurotransmitter precursor. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function.

Treatment: folinic acid

Non-genetic confirmatory testing: cerebrospinal fluid 5-methyltetrahydrofolate level
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1950 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1950 FCHO1 Zornitza Stark Classified gene: FCHO1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1950 FCHO1 Zornitza Stark Gene: fcho1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1949 FCHO1 Zornitza Stark gene: FCHO1 was added
gene: FCHO1 was added to Baby Screen+ newborn screening. Sources: Expert list
treatable, immunological tags were added to gene: FCHO1.
Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FCHO1 were set to 32098969; 30822429
Phenotypes for gene: FCHO1 were set to Immunodeficiency 76, MIM# 619164
Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data.

Immunodeficiency-76 (IMD76) is an autosomal recessive primary immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show T-cell lymphopenia and may show variable B-cell or immunoglobulin abnormalities. More variable features found in some patients include lymphoma and neurologic features.

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile, immunoglobulin levels
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1948 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1948 FAM111A Zornitza Stark Classified gene: FAM111A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1948 FAM111A Zornitza Stark Gene: fam111a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1947 FAM111A Zornitza Stark gene: FAM111A was added
gene: FAM111A was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: FAM111A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FAM111A were set to Kenny-Caffey syndrome, type 2, MIM# 127000
Review for gene: FAM111A was set to GREEN
Added comment: Condition is characterised by impaired skeletal development with small and dense bones, short stature, ocular abnormalities, and primary hypoparathyroidism with hypocalcemia. At least 10 unrelated cases reported with de novo missense variants. Intellectual disability/developmental delay is a rare feature of the condition.

Treatment: magnesium, calcium and calcitriol or alfacalcidol

Non-genetic confirmatory testing: serum calcium, parathyroid hormone level, calcitonin level
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1946 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1946 ERCC6L2 Zornitza Stark Classified gene: ERCC6L2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1946 ERCC6L2 Zornitza Stark Gene: ercc6l2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1944 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1944 DOCK2 Zornitza Stark Classified gene: DOCK2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1944 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1943 DOCK2 Zornitza Stark gene: DOCK2 was added
gene: DOCK2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DOCK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK2 were set to 26083206; 29204803; 33928462; 30826364; 30838481; 11518968
Phenotypes for gene: DOCK2 were set to Immunodeficiency 40 MIM# 616433
Review for gene: DOCK2 was set to GREEN
Added comment: 13 unrelated individuals; two mouse models; 10 biallelic mutations found (6 led to premature termination of the protein & 4 missense mutations affecting conserved residues) All patients presented with combined immunodeficiency in infancy (defective IFN-mediated immunity), early onset of invasive bacterial and viral infections, functional defects in T/B/NK cells and elevated IgM (normal IgG/IgA).

Treatment: bone marrow transplant.

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1942 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1942 DNASE2 Zornitza Stark Classified gene: DNASE2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1942 DNASE2 Zornitza Stark Gene: dnase2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1941 DNASE2 Zornitza Stark gene: DNASE2 was added
gene: DNASE2 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNASE2 were set to 29259162; 31775019
Phenotypes for gene: DNASE2 were set to Autoinflammatory-pancytopenia syndrome, MIM# 619858
Review for gene: DNASE2 was set to GREEN
Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data.

Treatment: baricitinib

Non-genetic confirmatory testing: Interferon signature
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1940 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1940 DNAJC21 Zornitza Stark Classified gene: DNAJC21 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1940 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1939 DNAJC21 Zornitza Stark gene: DNAJC21 was added
gene: DNAJC21 was added to Baby Screen+ newborn screening. Sources: Expert Review
Mode of inheritance for gene: DNAJC21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC21 were set to 29700810; 28062395; 27346687
Phenotypes for gene: DNAJC21 were set to Bone marrow failure syndrome 3, MIM# 617052
Review for gene: DNAJC21 was set to GREEN
Added comment: Onset of pancytopenia in early childhood; variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies.

Treatment: oral pancreatic enzymes, fat-soluble vitamins, blood and/or platelet transfusions, granulocyte-colony stimulation factor, bone marrow transplant

Confirmatory non-genetic testing: no; FBE as pancytopenia evolves.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1938 CYP2R1 Zornitza Stark Gene: cyp2r1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1938 CYP2R1 Zornitza Stark Classified gene: CYP2R1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1938 CYP2R1 Zornitza Stark Gene: cyp2r1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1936 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1936 C17orf62 Zornitza Stark Classified gene: C17orf62 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1936 C17orf62 Zornitza Stark Gene: c17orf62 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1935 C17orf62 Zornitza Stark gene: C17orf62 was added
gene: C17orf62 was added to Baby Screen+ newborn screening. Sources: Expert Review
new gene name, treatable, immunological tags were added to gene: C17orf62.
Mode of inheritance for gene: C17orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C17orf62 were set to 30361506; 30312704; 28351984
Phenotypes for gene: C17orf62 were set to Chronic granulomatous disease 5, autosomal recessive, MIM# 618935
Review for gene: C17orf62 was set to GREEN
Added comment: Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)

Primary immunodeficiency characterized by onset of recurrent infections and severe colitis in the first decade of life. Patients often present with features of inflammatory bowel disease and may show granulomata on biopsy. Patients are particularly susceptible to catalase-positive organisms, including Burkholderia cepacia, Legionella, and Candida albicans. Some patients may develop autoinflammatory symptoms, including recurrent fever in the absence of infection, hemolytic anemia, and lymphopenia. Additional features may include short stature, viral infections, cutaneous abscesses, pulmonary infections, and lymphadenitis. Haematopoietic bone marrow transplant is curative.

Non-genetic confirmatory assay: dihydrorhodamine assay
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1934 CYB561 Zornitza Stark Gene: cyb561 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1934 CYB561 Zornitza Stark Classified gene: CYB561 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1934 CYB561 Zornitza Stark Gene: cyb561 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1933 CYB561 Zornitza Stark gene: CYB561 was added
gene: CYB561 was added to Baby Screen+ newborn screening. Sources: Expert list
Mode of inheritance for gene: CYB561 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB561 were set to 29343526; 31822578
Phenotypes for gene: CYB561 were set to Orthostatic hypotension 2, MIM# 618182
Review for gene: CYB561 was set to GREEN
Added comment: Three families reported.

Severe orthostatic hypotension, recurrent hypoglycemia, and low norepinephrine levels. The disorder has onset in infancy or early childhood.

Treatment: L-threo-3,4-dihydroxyphenylserine (droxidopa)

Non-genetic confirmatory testing: plasma norepinephrine, epinephrine, dopamine
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1931 CR2 Zornitza Stark Gene: cr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1930 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1930 CORO1A Zornitza Stark Classified gene: CORO1A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1930 CORO1A Zornitza Stark Gene: coro1a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1929 CORO1A Zornitza Stark gene: CORO1A was added
gene: CORO1A was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CORO1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CORO1A were set to Immunodeficiency 8 MIM# 615401
Review for gene: CORO1A was set to GREEN
Added comment: 3 unrelated families and 1 unrelated individual reported with bi-allelic (deletion, missense, insertion) variants, resulting in premature stop codons and truncated protein/ alter a highly conserved residue in binding domain; one mouse model

All patients displayed T−B+NK+ SCID or CID presenting in early-onset recurrent infections and additional features that included EBV-associated lymphoproliferative disease and low immunoglobulin levels.

Congenital onset.

Treatment: bone marrow transplant

Non-genetic confirmatory testing: T and B Lymphocyte and Natural Killer Cell Profile
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1928 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1928 CDCA7 Zornitza Stark Classified gene: CDCA7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1928 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1927 CDCA7 Zornitza Stark gene: CDCA7 was added
gene: CDCA7 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CDCA7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDCA7 were set to 26216346
Phenotypes for gene: CDCA7 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 3, MIM# 616910
Review for gene: CDCA7 was set to GREEN
Added comment: Congenital onset, severe disorder. At least 4 unrelated families reported.

Treatment: replacement immunoglobulins, bone marrow transplant

Non-genetic confirmatory testing: immunoglobulin levels, cytogenetic analysis for centromeric instability, DNA methylation studies
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1926 CD81 Zornitza Stark Gene: cd81 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1926 CD81 Zornitza Stark gene: CD81 was added
gene: CD81 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD81 were set to 20237408
Phenotypes for gene: CD81 were set to Immunodeficiency, common variable, 6, MIM# 613496
Review for gene: CD81 was set to RED
Added comment: CVID, which would be congenital, severe and treatable with replacement immunoglobulins.

However, only a single individual reported.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1925 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1925 CD70 Zornitza Stark Classified gene: CD70 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1925 CD70 Zornitza Stark Gene: cd70 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1923 CD55 Zornitza Stark Gene: cd55 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1923 CD55 Zornitza Stark Classified gene: CD55 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1923 CD55 Zornitza Stark Gene: cd55 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1922 CD55 Zornitza Stark gene: CD55 was added
gene: CD55 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CD55 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD55 were set to 33398182
Phenotypes for gene: CD55 were set to Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300
Review for gene: CD55 was set to GREEN
Added comment: Severe congenital disorder, high mortality.

Treatment: Eculizumab

Non-genetic confirmatory testing: albumin level, immunoglobulin level
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1921 CD40 Zornitza Stark Classified gene: CD40 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1921 CD40 Zornitza Stark Gene: cd40 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1920 CD40 Zornitza Stark gene: CD40 was added
gene: CD40 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: CD40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD40 were set to 29884852
Phenotypes for gene: CD40 were set to Immunodeficiency with hyper-IgM, type 3, MIM# 606843
Review for gene: CD40 was set to GREEN
Added comment: Severity can be variable but generally congenital onset, and predisposition to severe infections. Note CD40L already included.

Treatment: bone marrow transplantation.

Non-genetic confirmatory testing: immunoglobulin levels, flow cytometric analysis
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1919 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1919 CD3G Zornitza Stark Classified gene: CD3G as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1919 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1917 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1917 CD27 Zornitza Stark Classified gene: CD27 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1917 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1915 CD247 Zornitza Stark Gene: cd247 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1915 CD247 Zornitza Stark Classified gene: CD247 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1915 CD247 Zornitza Stark Gene: cd247 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1913 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1913 CD19 Zornitza Stark Classified gene: CD19 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1913 CD19 Zornitza Stark Gene: cd19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1911 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1911 CAV1 Zornitza Stark Classified gene: CAV1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1911 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1908 PRDX1 Zornitza Stark Gene: prdx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1908 PRDX1 Zornitza Stark Classified gene: PRDX1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1908 PRDX1 Zornitza Stark Gene: prdx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1907 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1907 PNP Zornitza Stark Classified gene: PNP as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1907 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1906 MTHFR Zornitza Stark Gene: mthfr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1904 MTHFR Zornitza Stark Classified gene: MTHFR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1904 MTHFR Zornitza Stark Gene: mthfr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1903 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1901 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1899 MCCC1 Zornitza Stark Classified gene: MCCC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1899 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1898 MAT1A Zornitza Stark Gene: mat1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1896 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1892 LIAS Zornitza Stark Classified gene: LIAS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1892 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1891 HPD Zornitza Stark Gene: hpd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1890 HPD Zornitza Stark reviewed gene: HPD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tyrosinemia, type III MIM#276710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1890 HMGCS2 Zornitza Stark Gene: hmgcs2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1890 HMGCS2 Zornitza Stark Classified gene: HMGCS2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1890 HMGCS2 Zornitza Stark Gene: hmgcs2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1889 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1889 HIBCH Zornitza Stark Phenotypes for gene: HIBCH were changed from Neurodegeneration, progressive infantile to 3-hydroxyisobutryl-CoA hydrolase deficiency MIM#250620
Genomic newborn screening: BabyScreen+ v0.1887 HIBCH Zornitza Stark Classified gene: HIBCH as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1887 HIBCH Zornitza Stark Gene: hibch has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1886 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1884 GLIS3 Zornitza Stark Classified gene: GLIS3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1884 GLIS3 Zornitza Stark Gene: glis3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1883 PRDX1 Lilian Downie gene: PRDX1 was added
gene: PRDX1 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PRDX1 was set to Other
Publications for gene: PRDX1 were set to PMID: 20301503, PMID: 29396438, PMID: 34215320, PMID: 33982424
Phenotypes for gene: PRDX1 were set to Methylmalonic aciduria and homocystinuria, cblC type, digenic MIM#277400
Review for gene: PRDX1 was set to GREEN
Added comment: Digenic inheritance with mutation in other allele of MMACHC
On GUARDIAN and Rx genes list

Recently, three individuals who are double heterozygous for pathogenic variants in MMACHC and PRDX1 have been identified. PRDX1 is a neighboring gene on chromosome 1 transcribed from the reverse strand. Variants identified in PRDX1 located at the intron 5 splice acceptor site caused skipping of exon 6, transcription of antisense MMACHC, and hypermethylation of the MMACHC promoter/exon 1, resulting in no gene expression from that allele [Guéant et al 2018].

Treatable with cobalamin, carnitine & diet. NB MMACHC is green on our list, on newborn screening.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1883 PNP Lilian Downie gene: PNP was added
gene: PNP was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNP were set to PMID: 35968787, PMID: 35063692, PMID: 30885031, PMID: 1931007, PMID: 28674683
Phenotypes for gene: PNP were set to Immunodeficiency due to purine nucleoside phosphorylase deficiency MIM#613179
Review for gene: PNP was set to GREEN
Added comment: Decreased T cell function - SCID immunodeficiency
variable neurological phenotype
childhood onset
Treat bone marrow transplant
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1883 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1883 GATM Zornitza Stark Classified gene: GATM as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1883 GATM Zornitza Stark Gene: gatm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1882 FOXE1 Zornitza Stark Gene: foxe1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1880 FOXE1 Zornitza Stark Classified gene: FOXE1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1880 FOXE1 Zornitza Stark Gene: foxe1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1879 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1877 ALDH4A1 Zornitza Stark Classified gene: ALDH4A1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1877 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1876 ACADSB Zornitza Stark Gene: acadsb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1875 ACADS Zornitza Stark Gene: acads has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1875 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1873 ABCD4 Zornitza Stark Classified gene: ABCD4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1873 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1872 LIAS Lilian Downie gene: LIAS was added
gene: LIAS was added to gNBS. Sources: Expert list
Mode of inheritance for gene: LIAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIAS were set to PMID: 24334290, 24777537,
Phenotypes for gene: LIAS were set to Hyperglycinemia, lactic acidosis, and seizures MIM#614462
Review for gene: LIAS was set to RED
Added comment: pyruvate dehydrogenase lipoic acid synthetase deficiency (PDHLD)
increased serum glycine and lactate in the first days of life, hypotonia, seizures, early death
No treatment
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1872 HPD Lilian Downie reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 9343288, PMID: 11916315, PMID: 32520295; Phenotypes: Tyrosinemia, type III MIM#276710; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1872 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1872 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Genomic newborn screening: BabyScreen+ v0.1871 TANGO2 Zornitza Stark Classified gene: TANGO2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1871 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1869 LAMP2 Zornitza Stark Classified gene: LAMP2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1869 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1868 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1867 NKX2-5 Zornitza Stark Classified gene: NKX2-5 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1867 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1865 TANGO2 Ari Horton changed review comment from: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review; to: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

PMID: 35568137

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4–9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504–600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events.

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1865 TANGO2 Ari Horton gene: TANGO2 was added
gene: TANGO2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Cardiomyopathy; Metabolic Crises; Arrhythmia; Neurodevelopmental
Penetrance for gene: TANGO2 were set to Complete
Review for gene: TANGO2 was set to GREEN
Added comment: Folate may assist with TANGO2
DOI: https://doi.org/10.21203/rs.3.rs-1778084/v1

While chronic symptoms are predominantly neurodevelopmental, metabolic stressors such as fasting, dehydration, illness, and excessive heat can trigger episodic metabolic crises characterized by encephalopathy, ataxia, muscle weakness, rhabdomyolysis, and hypoglycemia. During these events, patients can develop acute life-threatening cardiac arrhythmias. Arrhythmias typically initiate with isolated premature ventricular contractions (PVC) followed by recalcitrant ventricular tachycardia. Because these lethal arrhythmias usually do not respond to standard antiarrhythmic therapies, cardiac arrhythmias are the leading cause of death in TDD

Fasting and feeding recommendations to reduce crises and improve cardiac status and neurodev outcomes, reduce risk of cardiac arrhythmias and SCDY

Natural history study (ClinicalTrials.gov Identifier: NCT05374616) strongly suggests that subjects on a multivitamin or a Bcomplex vitamin supplement have a greatly reduced risk for metabolic crises and cardiac arrhythmias

Specific diet and fasting plans are recommended for all patients from the neonatal period
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1865 MCFD2 Zornitza Stark Classified gene: MCFD2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1865 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1864 HBB Zornitza Stark Phenotypes for gene: HBB were changed from Sickle cell anaemia, MIM# 603903; Thalassaemia, beta, MIM# 613985 to Sickle cell anaemia, MIM# 603903
Genomic newborn screening: BabyScreen+ v0.1863 HBB Zornitza Stark edited their review of gene: HBB: Changed phenotypes: Sickle cell anaemia, MIM# 603903
Genomic newborn screening: BabyScreen+ v0.1863 RUNX1 Zornitza Stark Classified gene: RUNX1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1863 RUNX1 Zornitza Stark Gene: runx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1862 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1862 HBB Zornitza Stark changed review comment from: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.; to: Well established gene-disease associations.

Congenital onset.

Both sickle cell anaemia and beta thalassaemia are treatable disorders.

Beta thal: gene therapy (betibeglogene autotemcel - clinical trial), red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), Luspatercept

Sickle cell: glutamine, voxelotor, crizanlizumab, hydroxyurea, ,red cell transfusions, bone marrow transplantation (Hematopoietic Stem Cell Transplantation (HSCT)), gene therapy (BCH-BB694 BCL11A shmiR lentiviral vector - clinical trial and autologous CRISPR-Cas9-edited CD34+ hematopoietic stem and progenitor cells) - clinical trial)

Some of the beta-that variants are structural -- ability to detect reliably? For review.

We are only able to reliably screen for the HbS association.
Genomic newborn screening: BabyScreen+ v0.1862 HBA2 Zornitza Stark Classified gene: HBA2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1862 HBA2 Zornitza Stark Gene: hba2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1861 HBA1 Zornitza Stark Classified gene: HBA1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1861 HBA1 Zornitza Stark Gene: hba1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1860 HBA1 Zornitza Stark changed review comment from: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose? For review.; to: Well established gene-disease association.

Congenital onset.

Treatable: transfusions, bone marrow transplant.

However, there is widespread screening in pregnancy. Also note mutational spectrum includes SVs/CNVs: can we reliably diagnose?

Exclude for now due to technical concerns.
Genomic newborn screening: BabyScreen+ v0.1860 F8 Zornitza Stark Classified gene: F8 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1860 F8 Zornitza Stark Gene: f8 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1859 F8 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. For review.; to: Well established gene-disease association.

Variable severity.

Treatment: recombinant factor VIII. Gene therapy trial.

Non-genetic confirmatory testing: factor VIII levels.

Note: excluded from other screening tests due to concerns regarding ability to detect the intron 22 inversion (Inv22) mutation of F8 which causes about 45% of severe HA cases. Intron 1 inversion also common.

Excluded for now until we can confirm we can detect inversion.
Genomic newborn screening: BabyScreen+ v0.1859 TBX1 Zornitza Stark Classified gene: TBX1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1859 TBX1 Zornitza Stark Gene: tbx1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1858 PRKG1 Zornitza Stark Classified gene: PRKG1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1858 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1857 MYH11 Zornitza Stark Classified gene: MYH11 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1857 MYH11 Zornitza Stark Gene: myh11 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1856 LOX Zornitza Stark Classified gene: LOX as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1856 LOX Zornitza Stark Gene: lox has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1855 KCNQ1 Zornitza Stark Classified gene: KCNQ1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1855 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1853 JUP Zornitza Stark Classified gene: JUP as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1853 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1851 DSP Zornitza Stark Classified gene: DSP as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1851 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1849 TMEM43 Zornitza Stark changed review comment from: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.; to: Rated as 'strong actionability' in paediatric patients by ClinGen together with other ARVC genes.

ARVC is a progressive heart disease characterized by degeneration of cardiac myocytes and their subsequent replacement by fat and fibrous tissue primarily in the right ventricle, though the left ventricle may also be affected. It is associated with an increased risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) in young individuals and athletes. The VA is usually in proportion to the degree of ventricular remodeling and dysfunction, and electrical instability. The mechanism of SCD is cardiac arrest due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Age of onset is highly variable with a mean age of diagnosis of 31 years and a range of 4 to 64 years.

Antiarrhythmic drugs and beta-blockers are not recommended in healthy gene carriers. In patients with ARVC and ventricular arrhythmia (VA), a beta-blocker or other antiarrhythmic is recommended.

Recommendations for ICD placement in patients with ARVC differ across guidelines, both in terms of the indications for placement and whether recommendations are based on evidence or expert opinion. Recommendations based on non-randomized studies support ICD placement in patients with ARVC and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT hemodynamically tolerated, and significant ventricular dysfunction with RVEF or LVEF ≤35%) and in patients with ARVC and syncope presumed to be due to VA if meaningful survival greater than 1 year is expected. The presence of a combination of other risk factors (e.g., male sex, frequent PVCs, syncope) may also be used to indicate implantation.

Serial screening for the emergence of cardiomyopathy is recommended for clinically unaffected individuals who carry a variant associated with ARVC, including:

• Medical history, with special attention to heart failure symptoms, arrhythmias, presyncope or syncope, and thromboembolism
• Physical examination with special attention to cardiac and neuromuscular systems and examination of the integumentary system if ARVC is suspected
• Electrocardiography
• Cardiovascular imaging.

Penetrance:
In a study of 264 probands with genetic variants associated with ARVC who presented alive, 73% had sustained VA, 13% had symptomatic HF, and 5% had cardiac death (2% SCD, 2% HF, and 1% HF with VA) during median 8-year follow-up. Among 385 family members of the probands who also carried an ARVC variant, 32% met clinical criteria for ARVC, 11% experienced sustained VA, and 2% died during follow-up (1% from SCD, 0.5% from HF, and 0.5% non-cardiac issues). In a second study of 220 probands with genetic variants associated with ARVC who presented alive, 54% presented with sustained VT. In 321 family members of the probands who also carried an ARVC variant, 14% were symptomatic at presentation but 8% experienced VA during a mean 4-year follow-up. For all 541 cases, 60% met clinical criteria for ARVC, 30% had sustained VA, 14% developed ventricular dysfunction, 5% experienced HF, 4% had a resuscitated SCD/VF, and 2% died over a mean follow-up of 6 years.

Note founder variant in Newfoundland.
Genomic newborn screening: BabyScreen+ v0.1849 SCN5A Zornitza Stark Classified gene: SCN5A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1849 SCN5A Zornitza Stark Gene: scn5a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1848 KCNH2 Zornitza Stark Classified gene: KCNH2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1848 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1846 CASQ2 Zornitza Stark Classified gene: CASQ2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1846 CASQ2 Zornitza Stark Gene: casq2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1845 ACTA2 Zornitza Stark Classified gene: ACTA2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1845 ACTA2 Zornitza Stark Gene: acta2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1844 CAD Zornitza Stark Gene: cad has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1844 CAD Zornitza Stark Classified gene: CAD as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1844 CAD Zornitza Stark Gene: cad has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1843 CAD Zornitza Stark gene: CAD was added
gene: CAD was added to gNBS. Sources: Expert list
treatable, metabolic tags were added to gene: CAD.
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 28007989
Phenotypes for gene: CAD were set to Developmental and epileptic encephalopathy 50, MIM# 616457
Review for gene: CAD was set to GREEN
Added comment: Developmental and epileptic encephalopathy-50 (DEE50) is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset refractory seizures, severe developmental regression, and normocytic anemia. Onset is within the first months or years of life.

Affected children can have a favourable response to treatment with uridine, PMID 28007989
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1842 CA12 Zornitza Stark Gene: ca12 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1842 CA12 Zornitza Stark Classified gene: CA12 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1842 CA12 Zornitza Stark Gene: ca12 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1841 CA12 Zornitza Stark gene: CA12 was added
gene: CA12 was added to gNBS. Sources: Expert Review
treatable, metabolic tags were added to gene: CA12.
Mode of inheritance for gene: CA12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CA12 were set to Hyperchlorhidrosis, isolated MIM#143860
Review for gene: CA12 was set to GREEN
Added comment: Glu143Lys found in 4 Israeli Bedouin families. 2 other unrelated families reported with 1 missense (LoF demonstrated), 1 splice (aberrant splicing proven) and 1 fs (protein truncating, not NMD).

Excessive salt wasting in sweat can result in severe infantile hyponatraemic dehydration and hyperkalaemia.

Treatment: sodium chloride supplementation
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1840 AICDA Zornitza Stark Gene: aicda has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1840 AICDA Zornitza Stark Classified gene: AICDA as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1840 AICDA Zornitza Stark Gene: aicda has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1838 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1838 AGPAT2 Zornitza Stark Classified gene: AGPAT2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1838 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1837 AGPAT2 Zornitza Stark gene: AGPAT2 was added
gene: AGPAT2 was added to gNBS. Sources: Expert list
for review, treatable, endocrine tags were added to gene: AGPAT2.
Mode of inheritance for gene: AGPAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT2 were set to 29704234
Phenotypes for gene: AGPAT2 were set to Lipodystrophy, congenital generalized, type 1, MIM# 608594
Review for gene: AGPAT2 was set to AMBER
Added comment: Established gene-disease association.

Congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, is a rare autosomal recessive disease characterized by a near absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biologic features include acanthosis nigricans, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia.

Leptin replacement therapy (metreleptin) has been found to improve metabolic parameters in many patients with lipodystrophy. Metreleptin is approved in the United States as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy and has been submitted for approval elsewhere.

For review regarding availability and use of treatment locally.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1836 APC Zornitza Stark Classified gene: APC as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1836 APC Zornitza Stark Gene: apc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1835 WT1 Zornitza Stark Classified gene: WT1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1835 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1834 WT1 Zornitza Stark changed review comment from: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.

Penetrance is unclear. For review.; to: Rated as 'moderate actionability' in paediatric patients by ClinGen.

Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age. The median age of diagnosis is between 3 and 4 years and both kidneys are affected in ~5% of children. Significantly more females than males have the bilateral disease. Adult forms are very rare. In the majority of cases, the prognosis is favorable with a survival rate of over 90%.

The goal of surveillance in individuals with a genetic predisposition to WT is to

detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk. WTs can double in size every week, leading to the recommendation that evaluation with abdominal ultrasound be performed every 3-4 months, with and no less frequently than 3 times a year, until age five years. Even at this frequency, occasional tumors may present clinically between scans and families should be made aware of this. However, there is no evidence to suggest that such tumors have a worse outcome.

No evidence was found on the effectiveness of surveillance in children with WT due to WT1 pathogenic variants. In addition, there is no clear evidence that surveillance results in a significant decrease in mortality or tumor stage generally. However, tumors detected by surveillance would be anticipated to be on average smaller than tumors that present clinically. There have been three small retrospective evaluations of WT surveillance published, only one of which reported a significant difference in stage distribution between screened and unscreened individuals. This report was a case series of children with Beckwith-Wiedemann syndrome and idiopathic hemihypertropy, where 0/12 screened children with WT had late-stage disease and 25/59 (42%) of unscreened children had late-stage WT (p<0.003). In addition, in Germany, where abdominal ultrasound in children is common and 10% of WT are diagnosed prior to symptoms, there are some data to suggest that asymptomatic tumors are of lower stage than those present due to clinical symptoms.
Genomic newborn screening: BabyScreen+ v0.1834 GLA Zornitza Stark changed review comment from: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started. Note ERT is licensed in Australia from age 7 years.

However, carbamazepine relieves neuropathic pain, which has onset in early childhood. Overall, include.
Genomic newborn screening: BabyScreen+ v0.1834 SMAD2 Zornitza Stark Gene: smad2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1834 SMAD2 Zornitza Stark Classified gene: SMAD2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1834 SMAD2 Zornitza Stark Gene: smad2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1833 SMAD2 Zornitza Stark gene: SMAD2 was added
gene: SMAD2 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, MIM# 619656
Review for gene: SMAD2 was set to GREEN
Added comment: 9 individuals from 5 unrelated families reported with LDS phenotype. Gene-disease association rated 'moderate' by ClinGen but this gene is included in our diagnostic testing.

LDS included in gNBS panel as in general medical actionability for the LDS group of disorders is considered established.

Can manifest in early childhood.

Treatment: different interventions, including beta-blockers, surgical and monitoring

Non-genetic confirmatory test: characteristic clinical findings
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1832 PMS2 Zornitza Stark Classified gene: PMS2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1832 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1831 MSH6 Zornitza Stark Classified gene: MSH6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1831 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1830 MSH2 Zornitza Stark Classified gene: MSH2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1830 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1829 MLH1 Zornitza Stark Classified gene: MLH1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1829 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1828 SLC13A5 Zornitza Stark Classified gene: SLC13A5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1828 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1827 PTCH1 Zornitza Stark Classified gene: PTCH1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1827 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1826 PMM2 Zornitza Stark Classified gene: PMM2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1826 PMM2 Zornitza Stark Gene: pmm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1825 PIK3CA Zornitza Stark Classified gene: PIK3CA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1825 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1824 HPRT1 Zornitza Stark Classified gene: HPRT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1824 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1823 FBN1 Zornitza Stark Classified gene: FBN1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1823 FBN1 Zornitza Stark Gene: fbn1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1822 DICER1 Zornitza Stark Classified gene: DICER1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1822 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1821 RET Zornitza Stark changed review comment from: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: actionable in first 5 years of life?; to: Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: some actionability in first 5 years, variants can be stratified in terms of risk.
Genomic newborn screening: BabyScreen+ v0.1821 NF1 Zornitza Stark Classified gene: NF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1821 NF1 Zornitza Stark Gene: nf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1820 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1820 ECHS1 Zornitza Stark Classified gene: ECHS1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1820 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1818 DHFR Zornitza Stark Gene: dhfr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1818 DHFR Zornitza Stark Classified gene: DHFR as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1818 DHFR Zornitza Stark Gene: dhfr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1816 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1816 DNAJC12 Zornitza Stark Classified gene: DNAJC12 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1816 DNAJC12 Zornitza Stark Gene: dnajc12 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1814 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1814 GALM Zornitza Stark Classified gene: GALM as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1814 GALM Zornitza Stark Gene: galm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1812 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1812 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Dystonia, dopa-responsive to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230
Genomic newborn screening: BabyScreen+ v0.1809 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1809 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1808 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1807 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1805 PMS2 Zornitza Stark Classified gene: PMS2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1805 PMS2 Zornitza Stark Gene: pms2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1804 MSH6 Zornitza Stark Gene: msh6 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1802 MSH6 Zornitza Stark Classified gene: MSH6 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1802 MSH6 Zornitza Stark Gene: msh6 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1801 MLH1 Zornitza Stark changed review comment from: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer

•<10% develop cancer of other sites; to: Note mono-allelic variants are associated with adult-onset cancer risk.

MMRCS rated as 'strong actionability' in paediatric patients by ClinGen.

The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years.

The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested:

•Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended.
•Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age.
•Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years.
•Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician.
•For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years.
•Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years.
•To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI.

Estimated penetrance in MMRCS:

•50% develop small-bowel adenomas
•>90% develop colorectal adenomas
•59 to 70% develop colorectal cancer
•58 to 70% develop high-grade brain tumours
•20-40% develop lymphoma
•10-40% develop leukemia
•10 to 18% develop small-bowel cancer
•<10% develop endometrial cancer
•<10% develop urinary tract cancer
•<10% develop cancer of other sites
Genomic newborn screening: BabyScreen+ v0.1801 MLH1 Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1799 TMPRSS3 Seb Lunke Gene: tmprss3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1799 TMPRSS3 Seb Lunke Phenotypes for gene: TMPRSS3 were changed from Deafness, autosomal recessive to deafness, autosomal recessive MIM#601072
Genomic newborn screening: BabyScreen+ v0.1797 MSH2 Zornitza Stark Gene: msh2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1796 MLH1 Zornitza Stark Classified gene: MLH1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1796 MLH1 Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1794 MSH2 Zornitza Stark Classified gene: MSH2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1794 MSH2 Zornitza Stark Gene: msh2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1793 LYST Seb Lunke Gene: lyst has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1793 COL9A2 Seb Lunke Gene: col9a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1793 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1793 TPRN Zornitza Stark Phenotypes for gene: TPRN were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 79, MIM# 613307
Genomic newborn screening: BabyScreen+ v0.1792 TPRN Zornitza Stark Classified gene: TPRN as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1792 TPRN Zornitza Stark Gene: tprn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1791 TPRN Zornitza Stark reviewed gene: TPRN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 79, MIM# 613307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1791 STRC Zornitza Stark Classified gene: STRC as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1791 STRC Zornitza Stark Gene: strc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1790 STRC Zornitza Stark reviewed gene: STRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1790 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1790 S1PR2 Zornitza Stark Classified gene: S1PR2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1790 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1789 S1PR2 Zornitza Stark gene: S1PR2 was added
gene: S1PR2 was added to gNBS. Sources: ClinGen
deafness tags were added to gene: S1PR2.
Mode of inheritance for gene: S1PR2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: S1PR2 were set to Deafness, autosomal recessive 68, MIM# 610419
Review for gene: S1PR2 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen, onset of deafness is generally pre-lingual, therefore include.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1788 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1788 PTPRQ Zornitza Stark Classified gene: PTPRQ as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1788 PTPRQ Zornitza Stark Gene: ptprq has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1787 PTPRQ Zornitza Stark gene: PTPRQ was added
gene: PTPRQ was added to gNBS. Sources: ClinGen
deafness tags were added to gene: PTPRQ.
Mode of inheritance for gene: PTPRQ was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PTPRQ were set to Deafness, autosomal recessive 84A, MIM# 613391; Deafness, autosomal dominant 73, MIM# 617663
Review for gene: PTPRQ was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen, onset of deafness is generally pre-lingual, therefore include.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1786 POU3F4 Zornitza Stark Classified gene: POU3F4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1786 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1785 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1785 OTOG Zornitza Stark Phenotypes for gene: OTOG were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 18B - MIM#614945
Genomic newborn screening: BabyScreen+ v0.1784 OTOG Zornitza Stark Classified gene: OTOG as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1784 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1783 OTOG Zornitza Stark reviewed gene: OTOG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 18B - MIM#614945; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1783 MYO3A Zornitza Stark Classified gene: MYO3A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1783 MYO3A Zornitza Stark Gene: myo3a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1782 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1782 PRKG1 Zornitza Stark Classified gene: PRKG1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1782 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1781 PRKG1 Zornitza Stark gene: PRKG1 was added
gene: PRKG1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: PRKG1.
Mode of inheritance for gene: PRKG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKG1 were set to Aortic aneurysm, familial thoracic 8, MIM#615436
Penetrance for gene: PRKG1 were set to Incomplete
Review for gene: PRKG1 was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%).
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1780 MYH11 Zornitza Stark Gene: myh11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1779 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1779 LOX Zornitza Stark Classified gene: LOX as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1779 LOX Zornitza Stark Gene: lox has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1778 LOX Zornitza Stark gene: LOX was added
gene: LOX was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: LOX.
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, MIM#617168
Penetrance for gene: LOX were set to Incomplete
Review for gene: LOX was set to AMBER
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta).

Variable age of clinical presentation.

Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2.

Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol.

Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1777 ACTA2 Zornitza Stark Gene: acta2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1776 STK11 Zornitza Stark Classified gene: STK11 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1776 STK11 Zornitza Stark Gene: stk11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1775 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1774 MCEE Zornitza Stark Classified gene: MCEE as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1774 MCEE Zornitza Stark Gene: mcee has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1773 RUNX1 Zornitza Stark Gene: runx1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1773 RUNX1 Zornitza Stark Classified gene: RUNX1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1773 RUNX1 Zornitza Stark Gene: runx1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1772 RUNX1 Zornitza Stark gene: RUNX1 was added
gene: RUNX1 was added to gNBS. Sources: ClinGen
for review, treatable, haematological tags were added to gene: RUNX1.
Mode of inheritance for gene: RUNX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RUNX1 were set to Platelet disorder, familial, with associated myeloid malignancy, MIM# 601399
Review for gene: RUNX1 was set to AMBER
Added comment: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

HTHCPS is characterized by mild to moderate thrombocytopenia with normal platelet size, abnormal platelet functioning (defective release of delta granules and/or aggregation defects), and an increased risk of developing a haematologic malignancy.

Age of onset of bleeding can be highly variable, with some individuals presenting in early infancy and others not recognizing their symptoms until much later in life. Severe thrombocytopenia or profound platelet dysfunction can result in recognition during the perinatal or infancy period. Hematologic malignancies can occur in childhood or adulthood; the range of age of onset is wide with a median age of 33 years.

Use of clotting promotors (e.g., desmopressin, epsilon aminocaproic acid, tranexamic acid) can be used for surgeries, injuries, or dental treatments. Platelet transfusions may be used for severe bleeding or procedures with a high bleeding risk.

Though there is no specific treatment for HTHCPS, there are recommendations regarding the indications and timing of hematopoietic stem cell transplantation (HSCT) that vary. HSCT in pre-malignancy patients, particularly in the absence of any clonal progression, is debatable due to transplantation-associated risks and incomplete penetrance. Some suggested indications for HSCT include severe or symptomatic cytopenias, severe marrow dysplasia (particularly in the context of falling blood counts), complex or high-risk (e.g., monosomy 7) cytogenetic abnormalities (particularly if the clones are large or increasing in size) and increasing blasts >5%.

Consider use of a medical alert bracelet for thrombocytopenia, platelet dysfunction, or hematologic malignancy as indicated.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1771 DICER1 Zornitza Stark Gene: dicer1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1771 DICER1 Zornitza Stark Classified gene: DICER1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1771 DICER1 Zornitza Stark Gene: dicer1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1770 DICER1 Zornitza Stark gene: DICER1 was added
gene: DICER1 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to DICER1 syndrome, MONDO:0017288
Penetrance for gene: DICER1 were set to Incomplete
Review for gene: DICER1 was set to AMBER
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

A multiple registry study examining neoplasm incidence in a cohort containing 102 non-probands with DICER1 pathogenic variants (3,344 person-years of observation in non-probands) found that by age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of non-probands had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of non-probands had developed a neoplasm (females, 26.5%; males, 10.2%).

Most individuals with pathogenic variants in DICER1 are healthy or have only minor DICER1-associaited conditions. The most severe manifestations tend to present in early childhood with adulthood characterized by good health. The majority of tumors in individuals with DICER1 pathogenic variants occur in individuals younger than 40. Many of these tumors typically only occur in childhood, including: PPB (before age 7), CN (before age 4), CBME typically occurs in young children, pituitary blastoma (before age 2), and childhood pineoblastoma (only one has been reported associated with a DICER1 mutation).

Surveillance recommendations:
In order to detect pulmonary cysts or PPB (one of the most important causes of DICER1-associated morbidity and mortality), chest x-rays are recommended every 6 months from birth to through age 7 years and then annually from 8-12 years. A chest computed tomography (CT) (with efforts to minimize radiation) should be obtained by 9 months of age, preferably between 3 and 6 months of age and repeated at approximately 2.5 years of age.

Abdominal ultrasound is recommended for the detection in infancy or at the time of the first chest CT then every 6-12 months until at least 8 years of age. Annual ultrasound may be considered until 12 years of age.

Beginning at ages 8-10 females should receive pelvic ultrasound performed in conjunction with abdominal ultrasound (every 6-12 months) until at least age 40 or as needed for signs and symptoms.

Individuals should undergo thyroid ultrasound with assessment for regional adenopathy every 2 to 3 years starting at age 8 or as needed for signs and symptoms.

An annual routine dilated ophthalmologic exam with visual acuity screening is recommended from age 3 to at least age 10 for detection of CBME.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1769 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1767 BRCA1 Zornitza Stark Classified gene: BRCA1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1767 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1766 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1764 BRCA2 Zornitza Stark Classified gene: BRCA2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1764 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1763 KCNQ1 Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1762 KCNH2 Zornitza Stark Gene: kcnh2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1761 TMEM43 Zornitza Stark reviewed gene: TMEM43: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1761 PKP2 Zornitza Stark Gene: pkp2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1761 PKP2 Zornitza Stark Phenotypes for gene: PKP2 were changed from Arrhythmogenic right ventricular dysplasia 9 to Arrhythmogenic right ventricular dysplasia 9, MIM# 609040
Genomic newborn screening: BabyScreen+ v0.1760 PKP2 Zornitza Stark reviewed gene: PKP2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1760 DSP Zornitza Stark Gene: dsp has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1760 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Cardiomyopathy, dilated, with woolly hair and keratoderma, MIM# 605676; Epidermolysis bullosa, lethal acantholytic; Arrhythmogenic right ventricular dysplasia/cardiomyopathy; Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis , MIM#615821 to Arrhythmogenic right ventricular dysplasia 8, MIM# 607450
Genomic newborn screening: BabyScreen+ v0.1758 DSP Zornitza Stark reviewed gene: DSP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 8, MIM# 607450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1758 DSG2 Zornitza Stark Gene: dsg2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1758 DSG2 Zornitza Stark Phenotypes for gene: DSG2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 10, MIM# 610193
Genomic newborn screening: BabyScreen+ v0.1757 DSG2 Zornitza Stark reviewed gene: DSG2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 10, MIM# 610193; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1757 JUP Zornitza Stark Gene: jup has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1757 JUP Zornitza Stark Phenotypes for gene: JUP were changed from Arrhythmogenic right ventricular dysplasia 12; Naxos disease to Arrhythmogenic right ventricular dysplasia 12 MIM# 611528; Naxos disease MIM# 601214
Genomic newborn screening: BabyScreen+ v0.1756 JUP Zornitza Stark reviewed gene: JUP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 12 MIM# 611528, Naxos disease MIM# 601214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1756 DSC2 Zornitza Stark Gene: dsc2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1756 DSC2 Zornitza Stark Phenotypes for gene: DSC2 were changed from Arrhythmogenic right ventricular cardiomyopathy to Arrhythmogenic right ventricular dysplasia 11, MIM# 610476; Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476
Genomic newborn screening: BabyScreen+ v0.1754 DSC2 Zornitza Stark reviewed gene: DSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arrhythmogenic right ventricular dysplasia 11, MIM# 610476, Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair, MIM# 610476; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1754 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1754 OAT Zornitza Stark Classified gene: OAT as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1754 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1753 OAT Zornitza Stark gene: OAT was added
gene: OAT was added to gNBS. Sources: ClinGen
for review, treatable, metabolic tags were added to gene: OAT.
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia MIM#258870
Review for gene: OAT was set to GREEN
Added comment: Rated as 'moderate actionability' in paediatric patients by ClinGen.

GA due to deficiency of the enzyme ornithine aminotransferase (OAT) is characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. GA first presents as night blindness and constriction of the visual field caused by sharply demarcated circular areas of chorioretinal atrophy in the periphery. Atrophic areas progressively increase, coalesce, and spread towards the macula leading to central visual loss and blindness (vision less than 20/200).

Age at diagnosis ranges from 1 month to 44 years. The condition is characterized by the development of chorioretinal atrophic patches that start in the mid-peripheral retina in the first decade of life. Myopia, night blindness, changes in the macula (including cystic changes), and visual field affection usually start in the first or second decade. Most patients with GA have posterior subcapsular cataracts by the end of the second decade. Irreversible loss of vision and blindness generally occurs between 40 and 55 years of age but is highly variable.

Treatment of GA consists mainly of dietary modifications to help lower elevated systemic ornithine levels. Restriction of dietary arginine, a precursor of ornithine, appears to have therapeutic value. Pediatric patients undergoing arginine restriction should receive enough calories in their diet supplemented by essential amino acids, vitamins, and minerals to avoid malnutrition and excessive break down of endogenous proteins.

A long-term observational study of 27 patients with GA, 17 who complied with the arginine-restricted diet and 10 who were noncompliant, found that at 14 years follow-up the rates of vision loss were significantly slower in the compliant group for 3 of the 4 outcome measures, when adjusted for age.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1752 PCSK9 Zornitza Stark Gene: pcsk9 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1751 PCSK9 Zornitza Stark Classified gene: PCSK9 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1751 PCSK9 Zornitza Stark Gene: pcsk9 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1750 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489 to Carney complex, type 1, MIM# 160980
Genomic newborn screening: BabyScreen+ v0.1749 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1749 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1748 PRKAR1A Zornitza Stark edited their review of gene: PRKAR1A: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen, principally due to benefit from early detection of cardiac myxomas through surveillance.

CNC is associated with skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas.

Lentigines are the most common presenting feature of CNC and may be present at birth. Typically, they increase in number at puberty, fade after the fourth decade, but may still be evident in the eighth decade. Cutaneous myxomas appear between birth and the fourth decade. Cardiac myxomas may occur at a young age. Breast myxomas occur in females after puberty. Males and females may develop nipple myxomas at any age. In a minority of individuals, PPNAD presents in the first two to three years; in the majority, it presents in the second or third decade. LCCSCT often present in the first decade. Signs and symptoms of CNC may be present at birth, but the median age of diagnosis is 20 years. Most patients with CNC present with a mild increase in GH. However, clinically evident acromegaly is a relatively frequent manifestation of CNC, occurring in approximately 10% of adults at the time of presentation. Most individuals with CNC have a normal life span. However, because some die at an early age, the average life expectancy for individuals with CNC is 50 years. Causes of death include complications of cardiac myxoma (myxoma emboli, cardiomyopathy, cardiac arrhythmia, and surgical intervention), metastatic or intracranial PMS, thyroid carcinoma, and metastatic pancreatic and testicular tumors.

The only preventive measure in an asymptomatic individual is surgical removal of a heart tumor (cardiac myxoma) prior to the development of heart dysfunction, stroke, or other embolism. Cardiac myxomas should be diagnosed early through regular screening.

Development of metabolic abnormalities from Cushing syndrome or arthropathy and other complications from acromegaly may be prevented by medical or surgical treatment of the respective endocrine manifestations.

The overall penetrance of CNC in those with a PRKAR1A pathogenic variant is greater than 95% by age 50 years. 30-60% have cardiac myxomas.; Changed rating: GREEN; Changed phenotypes: Carney complex, type 1, MIM# 160980
Genomic newborn screening: BabyScreen+ v0.1748 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1747 RPS10 Zornitza Stark Classified gene: RPS10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1747 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1746 SCN5A Zornitza Stark Gene: scn5a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1746 SCN5A Zornitza Stark Phenotypes for gene: SCN5A were changed from Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome; Brugada syndrome 1, MIM# 601144; Long QT syndrome 3 (MIM#603830); Long QT syndrome; Heart block, progressive, type IA, MIM# 113900 to Long QT syndrome 3 (MIM#603830); Brugada syndrome 1, MIM# 601144
Genomic newborn screening: BabyScreen+ v0.1745 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from Pendred syndrome, MIM #274600 to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
Genomic newborn screening: BabyScreen+ v0.1744 SLC26A4 Zornitza Stark Classified gene: SLC26A4 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1744 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1743 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1743 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1743 TGFB3 Zornitza Stark Phenotypes for gene: TGFB3 were changed from Arrhythmogenic right ventricular dysplasia to Loeys-Dietz syndrome 5 , MIM#615582
Genomic newborn screening: BabyScreen+ v0.1742 TGFB3 Zornitza Stark Classified gene: TGFB3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1742 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1741 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1741 TGFB2 Zornitza Stark Classified gene: TGFB2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1741 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1740 TGFB2 Zornitza Stark gene: TGFB2 was added
gene: TGFB2 was added to gNBS. Sources: ClinGen
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4, MIM# 614816
Review for gene: TGFB2 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms which are the major source of morbidity and mortality. Aortic growth can be faster than 10mm per year. Aortic dissection has been observed in early childhood, and the mean age of death is 26 years. Other life-threatening manifestations include spontaneous rupture of the spleen, bowel, and uterine rupture during pregnancy.

Prophylactic surgical repair is typically recommended at an aortic diameter of ≥ 4.2 cm.

Beta-blockers or other medications can be used to reduce hemodynamic stress.

Consider Medicalert bracelet.

Use of subacute bacterial endocarditis prophylaxis should be considered for individuals with connective tissue disorders and documented evidence of mitral and/or aortic regurgitation who are undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria.

Because of a high risk of cervical spine instability, a flexion and extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1739 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1738 TRDN Zornitza Stark Classified gene: TRDN as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1738 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1737 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1737 TECRL Zornitza Stark Classified gene: TECRL as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1737 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1736 TECRL Zornitza Stark gene: TECRL was added
gene: TECRL was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: TECRL.
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1735 CALM3 Zornitza Stark Gene: calm3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1735 CALM3 Zornitza Stark Classified gene: CALM3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1735 CALM3 Zornitza Stark Gene: calm3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1734 CALM3 Zornitza Stark gene: CALM3 was added
gene: CALM3 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM3.
Mode of inheritance for gene: CALM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM3 were set to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM# 618782
Penetrance for gene: CALM3 were set to Incomplete
Review for gene: CALM3 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1733 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1733 CALM2 Zornitza Stark Classified gene: CALM2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1733 CALM2 Zornitza Stark Gene: calm2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1732 CALM2 Zornitza Stark gene: CALM2 was added
gene: CALM2 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM2.
Mode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM2 were set to Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990
Review for gene: CALM2 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1731 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1731 CALM1 Zornitza Stark Classified gene: CALM1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1731 CALM1 Zornitza Stark Gene: calm1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1730 CALM1 Zornitza Stark gene: CALM1 was added
gene: CALM1 was added to gNBS. Sources: ClinGen
for review, cardiac, treatable tags were added to gene: CALM1.
Mode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CALM1 were set to Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916
Penetrance for gene: CALM1 were set to Incomplete
Review for gene: CALM1 was set to GREEN
Added comment: Rated as 'strong actionability' for paediatric patients by ClinGen.

The mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.

Individuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.

Beta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.

In patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.

Clinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.

For review: age of onset and penetrance.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1729 RPE65 Zornitza Stark Gene: rpe65 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1729 RPE65 Zornitza Stark Classified gene: RPE65 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1729 RPE65 Zornitza Stark Gene: rpe65 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1728 RPE65 Zornitza Stark gene: RPE65 was added
gene: RPE65 was added to gNBS. Sources: ClinGen
for review, treatable, ophthalmological tags were added to gene: RPE65.
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794
Review for gene: RPE65 was set to GREEN
Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.

Biallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision.

In LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood.

In December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups.

LUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes).

For review: availability of therapy?
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1727 CP Zornitza Stark Gene: cp has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1726 WT1 Zornitza Stark Gene: wt1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1726 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome to Wilms tumor, type 1, MIM#194070
Genomic newborn screening: BabyScreen+ v0.1725 ITGB3 Zornitza Stark Gene: itgb3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1725 ITGB3 Zornitza Stark Classified gene: ITGB3 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1725 ITGB3 Zornitza Stark Gene: itgb3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1724 ITGB3 Zornitza Stark gene: ITGB3 was added
gene: ITGB3 was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGB3.
Mode of inheritance for gene: ITGB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGB3 were set to Glanzmann thrombasthenia 2, MIM# 619267
Review for gene: ITGB3 was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1723 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1723 ITGA2B Zornitza Stark Classified gene: ITGA2B as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1723 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1722 ITGA2B Zornitza Stark gene: ITGA2B was added
gene: ITGA2B was added to gNBS. Sources: ClinGen
treatable, haematological tags were added to gene: ITGA2B.
Mode of inheritance for gene: ITGA2B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800
Review for gene: ITGA2B was set to GREEN
Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen.

GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long.

Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.

The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.

Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting.
Sources: ClinGen
Genomic newborn screening: BabyScreen+ v0.1721 F7 Zornitza Stark changed review comment from: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level; to: Well established gene-disease association.

Variable severity.

Treatment: Recombinant coagulation Factor VIIa

Non-genetic confirmatory testing: factor VII level

Rated as 'strong actionability' in paediatric patients by ClinGen.

Clinical expression of factor VII deficiency is highly variable, and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. Individuals can be completely asymptomatic despite a very low FVII level. A bleeding history appears more predictive of further bleeding than the factor VII level. Factor VII levels increase during pregnancy, but levels usually remain insufficient for hemostasis in severely affected cases. Individuals with no history of bleeding do not appear to be at increased risk of PPH. Heterozygotes often have approximately half-normal levels of coagulation factors and are often asymptomatic. However, up to 2% of patients with severe bleeding phenotype are heterozygotes.

Consider prophylaxis using rFVIIa in certain circumstances. Long term prophylaxis should be considered for cases with a personal or family history of severe bleeding or with FVII activity <0.01 IU/ml using rFVIIa, adjusting to maintain clinical response. Short term prophylaxis should be considered for cases for neonates without a personal or family history of severe bleeding but who have FVII activity 0.01-0.05 IU/ml up to 6-12 months of age.
Genomic newborn screening: BabyScreen+ v0.1721 ABCC8 Zornitza Stark Gene: abcc8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1721 COL9A1 Zornitza Stark Gene: col9a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1721 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1720 TFAP2B Zornitza Stark Classified gene: TFAP2B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1720 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1719 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1718 TFAP2A Zornitza Stark Classified gene: TFAP2A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1718 TFAP2A Zornitza Stark Gene: tfap2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1717 TECTA Zornitza Stark Gene: tecta has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1717 TECTA Zornitza Stark Phenotypes for gene: TECTA were changed from Deafness to Deafness, autosomal recessive 21 603629; Deafness, autosomal dominant 8/12 601543
Genomic newborn screening: BabyScreen+ v0.1712 SI Zornitza Stark Tag treatable tag was added to gene: SI.
Tag gastrointestinal tag was added to gene: SI.
Genomic newborn screening: BabyScreen+ v0.1712 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1712 PSPH Zornitza Stark Gene: psph has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1711 PSPH Zornitza Stark Classified gene: PSPH as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1711 PSPH Zornitza Stark Gene: psph has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1710 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1710 COL9A1 David Amor changed review comment from: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome; to: Gene-disease association: strong but rare, prbably <1% of Sticller syndrome; Van Camp et al. (2006) described a consanguineous Moroccan family in which 4 of 10 sibs had features characteristic of Stickler syndrome, including moderate to severe sensorineural hearing loss, moderate to high myopia with vitreoretinopathy, and epiphyseal dysplasia. Nikopoulos et al. (2011) reported 2 sisters in a Turkish family and 1 boy in a Moroccan family with features of autosomal recessive Stickler syndrome. All 3 individuals had myopia, vitreous changes, sensorineural hearing loss, and epiphyseal dysplasia. They also had exudative rhegmatogenous retinal detachment.

Severity: moderate-severe

Age of onset: congenital

Non-molecular confirmatory testing: Affected individuals have moderate-to-severe sensorineural hearing loss, moderate-to-high myopia with vitreoretinopathy, cataracts, and epiphyseal dysplasia

Treatment: as per other Stickler syndrome
Genomic newborn screening: BabyScreen+ v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
Genomic newborn screening: BabyScreen+ v0.1710 ABCC8 David Amor commented on gene: ABCC8: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
Genomic newborn screening: BabyScreen+ v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
Genomic newborn screening: BabyScreen+ v0.1710 ABCC8 David Amor changed review comment from: Gene-disease association: strong. Note sporadic cases with focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele

Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes, glucose, insulin, free fatty acid levels

Treatment: as per rx-genes, Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus; to: Gene-disease association: strong. Note sporadic cases of Familial hyperinsulinemic hypoglycemiawith focal adenomatous hyperplasia due to paternally inherited variants focal loss of maternal allele.

ABCC8 associated permanent neonatal diabetes mellitus typically due to GoF missense variants. Fathers are at increased risk of T2DM also.



Severity: severe

Age of onset: congenital

Non-molecular confirmatory testing: yes
For hyperinsulinaemic hypoglycaemia: glucose, insulin, free fatty acid levels
For neonatal diabetes: glucose tolerance test, hemoglobin A1C, insulin level, glucose level

Treatment: as per rx-genes
For hyperinsulinaemic hypoglycaemia: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

For neonatal diabetes: Insulin, glibenclamide, oral pancreatic enzymes
Genomic newborn screening: BabyScreen+ v0.1710 TECTA David Amor reviewed gene: TECTA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 21, Deafness, autosomal dominant 8/12; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1710 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1710 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from X-linked hydrocephalus syndrome to Hydrocephalus due to aqueductal stenosis, MIM# 307000
Genomic newborn screening: BabyScreen+ v0.1709 L1CAM Zornitza Stark Classified gene: L1CAM as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1709 L1CAM Zornitza Stark Gene: l1cam has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1708 KCNJ11 Zornitza Stark changed review comment from: Association with hyperinsulinism is well established.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.; to: Association with hyperinsulinism is well established, mono-allelic variants.

Onset is congenital.

Treatment: Diazoxide, somatostatin analogs, nifedipine, glucagon, IGF-1, glucocorticoids, growth hormone, pancreatic resection, mTOR inhibitors, GLP-1 receptor antagonists, sirolimus

Association with neonatal diabetes is also well established, bi-allelic variants.

Treatment: Insulin, glibenclamide, oral pancreatic enzymes.

Phenotypes are expected to be distinguishable clinically.
Genomic newborn screening: BabyScreen+ v0.1708 KCNJ11 Zornitza Stark Gene: kcnj11 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1708 KCNJ11 Zornitza Stark Phenotypes for gene: KCNJ11 were changed from Hyperinsulinemic hypoglycemia, familial, MIM#601820 to Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820
Genomic newborn screening: BabyScreen+ v0.1706 KCNJ11 Zornitza Stark reviewed gene: KCNJ11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, transient neonatal, 3 610582, Diabetes, permanent neonatal, with or without neurologic features 606176, Hyperinsulinemic hypoglycemia, familial, 2 601820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1706 GNS Zornitza Stark Gene: gns has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1706 GNS Zornitza Stark Phenotypes for gene: GNS were changed from Mucopolysaccharidosis IIId to Mucopolysaccharidosis type IIID, MIM# 252940
Genomic newborn screening: BabyScreen+ v0.1704 GNS Zornitza Stark Classified gene: GNS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1704 GNS Zornitza Stark Gene: gns has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1702 GNAS Zornitza Stark Gene: gnas has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1702 GLRA1 Zornitza Stark Gene: glra1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1701 GLA Zornitza Stark changed review comment from: For review: screen only for males or include both?; to: Assessed as 'moderate actionability' in paediatric patients by ClinGen.

In classic FD, the first symptoms, including chronic neuropathic pain and episodic severe pain crises, emerge during childhood (typically age 3-10 years). Heterozygous females typically have a later median age of onset than males (9-13 years versus 13-23 years). Rarely, females may be relatively asymptomatic and have a normal life span or may have symptoms as severe as males with the classic phenotype.

Cardiac and/or cerebrovascular disease is present in most males by middle age while ESRD usually develops during the third to fifth decade. Renal and cardiac failure represent major sources of morbidity, and account for the reduced lifespan among affected males (50-58 years) and females (70-75 years) compared to the normal population.

A systematic review of RCTs of ERT reported on nine studies of 351 FD patients; however, many of these studies reported only on the effect of ERT on levels of enzyme substrate. Data from 2 trials (n=39 males) found no statistically significant differences in plasma enzyme substrate and one trial (n=24 males) found no statistical differences in renal function between individuals treated with agalsidase alfa and placebo (up to 6-month follow-up). Similar results were seen for agalsidase beta. One trial of 26 male patients found a statistically significant difference in pain, favoring agalsidase alfa compared to placebo at 5-6 months after treatment. No trial reported on the effect of agalsidase alfa on mortality or cardiac/cerebrovascular disease. One trial of agalsidase beta (n=82 males and females) found no difference in mortality, renal function, or symptoms or complications of cardiac or cerebrovascular disease over 18 months. The long-term influence of ERT on risk of morbidity and mortality related to FD remains to be established.

Migalastat, an oral chaperone drug, is recommended as an option for treatment for some patients with FD who are over 16 years with an amenable genetic variant who would usually be offered ERT. For non-amenable genotypes, migalastat may result in a net loss of alpha-Gal A activity, potentially worsening the disease condition.

A systematic review evaluated 2 phase III RCTs that both included males and females. One RCT randomized patients to switch from ERT to migalastat (n = 36) or continue with ERT (n = 24) during an 18-month period with a 12-month extension in which all patients received migalastat. During the treatment period, the percentage of patients who had a renal, cardiac, or cerebrovascular event or died was 29% of patients on migalastat compared to 44% of patients on ERT. However, this difference was not statistically significant. A second RCT compared migalastat (n=34) with placebo (n=33) over a 6-month period, with an 18-month extension study. The primary outcome was change from baseline in interstitial capillary inclusions of the enzyme substrate globotriaosylceramide (GL-3), which was not significantly different between groups. Results from both trials indicate that migalastat does not have a significant beneficial effect on pain, health-related quality of life outcomes, or glomerular filtration rate (results were uncertain due to large confidence intervals, small sample sizes, and/or short follow-up time). Migalastat did not influence left ventricular ejection fraction but did improve left ventricular mass over 18 months.

There are a number of recommendations for surveillance and agents to avoid (amiodarone). There is no consensus as to when ERT should be started.
Genomic newborn screening: BabyScreen+ v0.1701 GJB2 Zornitza Stark Gene: gjb2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1701 GJB2 Zornitza Stark Phenotypes for gene: GJB2 were changed from Deafness and palmoplantar keratoderma; Deafness to Deafness, autosomal recessive 1A, MIM# 220290
Genomic newborn screening: BabyScreen+ v0.1699 GJB2 Zornitza Stark reviewed gene: GJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 1A, MIM# 220290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1698 F9 Zornitza Stark Gene: f9 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1698 F8 Zornitza Stark Gene: f8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1698 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1698 FGF23 Zornitza Stark Gene: fgf23 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1698 FGF23 Zornitza Stark Classified gene: FGF23 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1698 FGF23 Zornitza Stark Gene: fgf23 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1697 FGF23 Zornitza Stark gene: FGF23 was added
gene: FGF23 was added to gNBS. Sources: Expert list
Mode of inheritance for gene: FGF23 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: FGF23 were set to autosomal dominant hypophosphatemic rickets MONDO:0008660; familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome MONDO:0100251
Review for gene: FGF23 was set to GREEN
Added comment: Mono-allelic GoF variants are associated with hypophosphataemic rickets.

Onset in some is in infancy (others adolescence).

Treatment: phosphate supplementation and calcitriol

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase levels, urine calcium level

Bi-allelic LoF variants are associated with tumoral calcinosis.

Age of onset and severity are variable, but include early childhood.

Treatment: dietary restriction, antacids, phosphate binders, acetazolamide, hemodialysis

Non-genetic confirmatory testing: serum phosphate, calcium, PTH, alkaline phosphatase, vitamin D serum levels, urine calcium, phosphate levels, plasma levels of the C-terminal portion of the phosphate-regulating hormone, fibroblast growth factor 23
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1696 F5 Zornitza Stark Gene: f5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1696 F5 Zornitza Stark Phenotypes for gene: F5 were changed from Factor V deficiency MIM# 227400; Thrombophilia due to activated protein C resistance MIM# 188055 to Factor V deficiency, MIM# 227400 MONDO:0009210; Thrombophilia due to activated protein C resistance, MIM# 188055 MONDO:0008560; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055
Genomic newborn screening: BabyScreen+ v0.1695 F5 Zornitza Stark Classified gene: F5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1695 F5 Zornitza Stark Gene: f5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1694 F5 Zornitza Stark reviewed gene: F5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency, MIM# 227400 MONDO:0009210, Thrombophilia due to activated protein C resistance, MIM# 188055 MONDO:0008560, {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1694 F2 Zornitza Stark Gene: f2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1692 F2 Zornitza Stark Classified gene: F2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1692 F2 Zornitza Stark Gene: f2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1691 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1691 F11 Zornitza Stark Gene: f11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1691 F11 Zornitza Stark Phenotypes for gene: F11 were changed from Factor XI deficiency to Factor XI deficiency, autosomal dominant 612416; Factor XI deficiency, autosomal recessive, MIM#612416
Genomic newborn screening: BabyScreen+ v0.1689 F11 Zornitza Stark Classified gene: F11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1689 F11 Zornitza Stark Gene: f11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1688 F11 Zornitza Stark reviewed gene: F11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor XI deficiency, autosomal dominant 612416, Factor XI deficiency, autosomal recessive, MIM#612416; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1688 DNAJB6 Zornitza Stark Classified gene: DNAJB6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1688 DNAJB6 Zornitza Stark Gene: dnajb6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1687 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1684 COL4A3 Zornitza Stark Gene: col4a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1684 COL4A3 Zornitza Stark Phenotypes for gene: COL4A3 were changed from Alport syndrome to Alport syndrome 2, autosomal recessive, MIM# 203780
Genomic newborn screening: BabyScreen+ v0.1682 COL4A3 Zornitza Stark reviewed gene: COL4A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 2, autosomal recessive, MIM# 203780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1682 COL4A4 Zornitza Stark Gene: col4a4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1682 COL4A4 Zornitza Stark Phenotypes for gene: COL4A4 were changed from Alport syndrome to Alport syndrome 2, autosomal recessive MIM#203780
Genomic newborn screening: BabyScreen+ v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.; to: Well established gene-disease association.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
Genomic newborn screening: BabyScreen+ v0.1681 COL4A4 Zornitza Stark changed review comment from: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.; to: Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Individuals with AR AS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria.
Genomic newborn screening: BabyScreen+ v0.1681 COL4A4 Zornitza Stark edited their review of gene: COL4A4: Changed rating: GREEN; Changed phenotypes: Alport syndrome 2, autosomal recessive MIM#203780; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1681 COL4A5 Zornitza Stark changed review comment from: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.

For review: screen both males and females?; to: Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.
Genomic newborn screening: BabyScreen+ v0.1681 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1680 COL3A1 Zornitza Stark Classified gene: COL3A1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1680 COL3A1 Zornitza Stark Gene: col3a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1679 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1677 CDAN1 Zornitza Stark Gene: cdan1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1676 CDAN1 Zornitza Stark Classified gene: CDAN1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1676 CDAN1 Zornitza Stark Gene: cdan1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1675 UROS John Christodoulou reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30685241; Phenotypes: hydros, photosensitivity, erythrodontia, corneal scarring, haemolytic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1675 TPP1 John Christodoulou reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30783219, PMID: 32280231; Phenotypes: neruodegeneration, seizures, loss of vision, loss of language; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1675 TFG Zornitza Stark Gene: tfg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1675 TFG Zornitza Stark Phenotypes for gene: TFG were changed from Hereditary motor and sensory neuropathy to Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484; Spastic paraplegia 57, autosomal recessive, MIM# 615658
Genomic newborn screening: BabyScreen+ v0.1673 TFG Zornitza Stark Classified gene: TFG as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1673 TFG Zornitza Stark Gene: tfg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1672 TFG Zornitza Stark reviewed gene: TFG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484, Spastic paraplegia 57, autosomal recessive, MIM# 615658; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1672 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1672 TG Zornitza Stark Phenotypes for gene: TG were changed from Thyroid dyshormonogenesis 3 to Thyroid dyshormonogenesis 3, MIM# 274700
Genomic newborn screening: BabyScreen+ v0.1670 TG Zornitza Stark reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 3, MIM# 274700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1670 TGM5 Zornitza Stark Gene: tgm5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1669 TGM5 Zornitza Stark Classified gene: TGM5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1669 TGM5 Zornitza Stark Gene: tgm5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1668 TGM1 Zornitza Stark Gene: tgm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1668 TGM1 Zornitza Stark Phenotypes for gene: TGM1 were changed from Ichthyosis, congenital, autosomal recessive to Ichthyosis, congenital, autosomal recessive 1 (MIM#242300)
Genomic newborn screening: BabyScreen+ v0.1667 TGM1 Zornitza Stark Classified gene: TGM1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1667 TGM1 Zornitza Stark Gene: tgm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1666 TGM1 Zornitza Stark reviewed gene: TGM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 1 (MIM#242300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1666 TGFBR2 Zornitza Stark Gene: tgfbr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1665 TGFBR1 Zornitza Stark Gene: tgfbr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1664 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1663 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1661 THRB Zornitza Stark Gene: thrb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1661 THRB Zornitza Stark Phenotypes for gene: THRB were changed from Thyroid hormone resistance to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Genomic newborn screening: BabyScreen+ v0.1659 THRB Zornitza Stark Classified gene: THRB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1659 THRB Zornitza Stark Gene: thrb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1658 THRB Zornitza Stark reviewed gene: THRB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1658 TIMM8A Zornitza Stark Gene: timm8a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1656 TIMM8A Zornitza Stark Classified gene: TIMM8A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1656 TIMM8A Zornitza Stark Gene: timm8a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1654 TK2 Zornitza Stark Gene: tk2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1653 TMC1 Zornitza Stark Gene: tmc1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1653 TMC1 Zornitza Stark Phenotypes for gene: TMC1 were changed from Deafness to Deafness, autosomal recessive 7 MIM#600974
Genomic newborn screening: BabyScreen+ v0.1651 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1651 TMEM43 Zornitza Stark Phenotypes for gene: TMEM43 were changed from Arrhythmogenic right ventricular dysplasia 5 to Arrhythmogenic right ventricular dysplasia 5 MIM#604400
Genomic newborn screening: BabyScreen+ v0.1649 TMEM43 Zornitza Stark Classified gene: TMEM43 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1649 TMEM43 Zornitza Stark Gene: tmem43 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1648 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1648 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from Joubert syndrome; Meckel syndrome to COACH syndrome MIM#216360; Joubert syndrome MIM#10688; Meckel syndrome MIM#607361; Nephronophthisis MIM#613550
Genomic newborn screening: BabyScreen+ v0.1646 TMEM67 Zornitza Stark Classified gene: TMEM67 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1646 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1645 TMIE Zornitza Stark Gene: tmie has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1645 TK2 John Christodoulou reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29602790, PMID: 31125140, PMID: 23385875; Phenotypes: myopathy, ophthalmoparesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1645 TMIE Zornitza Stark Phenotypes for gene: TMIE were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 6 MIM#600971
Genomic newborn screening: BabyScreen+ v0.1643 THRA John Christodoulou changed review comment from: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; to: Congenital nongoitrous hypothyroidism 6

normal TSH, so will be missed by NBS

treatment with thyroxine; others report that patients are resistant to thyroxine therapy (PMID: 28527577)
Genomic newborn screening: BabyScreen+ v0.1643 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1641 USH1C Zornitza Stark Gene: ush1c has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1639 USH1G Zornitza Stark Gene: ush1g has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1637 USH2A Zornitza Stark Gene: ush2a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1635 VCAN Zornitza Stark Gene: vcan has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1633 VCAN Zornitza Stark Classified gene: VCAN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1633 VCAN Zornitza Stark Gene: vcan has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1632 SLC25A19 John Christodoulou reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31095747; Phenotypes: recurrent encephalopathy, basal ganglia necrosis, generalized dystonia, polyneuropathy, ataxia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1632 PROS1 Zornitza Stark Gene: pros1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1632 PROS1 Zornitza Stark Phenotypes for gene: PROS1 were changed from Protein S deficiency to Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336; Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514
Genomic newborn screening: BabyScreen+ v0.1630 PROS1 Zornitza Stark Classified gene: PROS1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1630 PROS1 Zornitza Stark Gene: pros1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1629 PROS1 Zornitza Stark reviewed gene: PROS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336, Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1629 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1629 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1627 PROKR2 Zornitza Stark Classified gene: PROKR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1627 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1626 PROC Zornitza Stark Gene: proc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1626 PROC Zornitza Stark Phenotypes for gene: PROC were changed from Thrombophilia due to protein C deficiency to Thrombophilia due to protein C deficiency, autosomal dominant (176860); Thrombophilia due to protein C deficiency, autosomal recessive (612304)
Genomic newborn screening: BabyScreen+ v0.1624 PROC Zornitza Stark Classified gene: PROC as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1624 PROC Zornitza Stark Gene: proc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1623 PROC Zornitza Stark reviewed gene: PROC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia due to protein C deficiency, autosomal dominant (176860), Thrombophilia due to protein C deficiency, autosomal recessive (612304); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1623 PRKDC Zornitza Stark Gene: prkdc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1623 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1623 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from Carney complex to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
Genomic newborn screening: BabyScreen+ v0.1622 PRKAR1A Zornitza Stark Classified gene: PRKAR1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1622 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1621 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1621 PRF1 Zornitza Stark Gene: prf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1621 PRF1 Zornitza Stark edited their review of gene: PRF1: Changed phenotypes: Hemophagocytic lymphohistiocytosis, familial, 2 603553
Genomic newborn screening: BabyScreen+ v0.1621 PNPO Zornitza Stark Gene: pnpo has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1619 PPT1 Zornitza Stark Gene: ppt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1618 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from Neuronal ceroid lipofuscinosis to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730
Genomic newborn screening: BabyScreen+ v0.1617 PPT1 Zornitza Stark Classified gene: PPT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1617 PPT1 Zornitza Stark Gene: ppt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1616 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1615 POU4F3 Zornitza Stark Classified gene: POU4F3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1615 POU4F3 Zornitza Stark Gene: pou4f3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1614 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1613 POU3F4 Zornitza Stark Classified gene: POU3F4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1613 POU3F4 Zornitza Stark Gene: pou3f4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1612 POU1F1 Zornitza Stark Gene: pou1f1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1610 PORCN Zornitza Stark Gene: porcn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1610 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from Focal dermal hypoplasia to Focal dermal hypoplasia, MIM#305600
Genomic newborn screening: BabyScreen+ v0.1608 PORCN Zornitza Stark Classified gene: PORCN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1608 PORCN Zornitza Stark Gene: porcn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1607 PORCN Zornitza Stark reviewed gene: PORCN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal dermal hypoplasia, MIM#305600; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.1607 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1607 POR Zornitza Stark Phenotypes for gene: POR were changed from Disordered steroidogenesis with and without Antley-Bixler syndrome, MIM#201750 to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM# 613571
Genomic newborn screening: BabyScreen+ v0.1606 POR Zornitza Stark reviewed gene: POR: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM# 613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1606 POMT2 Zornitza Stark Gene: pomt2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1605 POMT2 Zornitza Stark Classified gene: POMT2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1605 POMT2 Zornitza Stark Gene: pomt2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1604 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1603 POMGNT1 Zornitza Stark Classified gene: POMGNT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1603 POMGNT1 Zornitza Stark Gene: pomgnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1602 POLH Zornitza Stark Gene: polh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1601 POLH Zornitza Stark Classified gene: POLH as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1601 POLH Zornitza Stark Gene: polh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1600 POLG Zornitza Stark Gene: polg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1600 POLG Zornitza Stark Phenotypes for gene: POLG were changed from POLG-Related Ataxia Neuropathy Spectrum Disorders to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450; Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640
Genomic newborn screening: BabyScreen+ v0.1597 POLG Zornitza Stark Classified gene: POLG as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1597 POLG Zornitza Stark Gene: polg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1596 POLG Zornitza Stark reviewed gene: POLG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700, Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459, Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450, Progressive external ophthalmoplegia, autosomal dominant 1, MIM# 157640; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1596 PNKP Zornitza Stark Gene: pnkp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1594 PNKP Zornitza Stark Classified gene: PNKP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1594 PNKP Zornitza Stark Gene: pnkp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1593 POMT1 Zornitza Stark Gene: pomt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1592 POMT1 Zornitza Stark Classified gene: POMT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1592 POMT1 Zornitza Stark Gene: pomt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1591 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1590 PQBP1 Zornitza Stark Classified gene: PQBP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1590 PQBP1 Zornitza Stark Gene: pqbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1589 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1589 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from Paroxysmal nonkinesiogenic dyskinesia to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800
Genomic newborn screening: BabyScreen+ v0.1588 PNKD Zornitza Stark Classified gene: PNKD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1588 PNKD Zornitza Stark Gene: pnkd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1587 PNKD Zornitza Stark reviewed gene: PNKD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1587 PMP22 Zornitza Stark Gene: pmp22 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1587 PMP22 Zornitza Stark Phenotypes for gene: PMP22 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, type 1A, MIM# 118220; Charcot-Marie-Tooth disease, type 1E, MIM# 118300; Dejerine-Sottas disease, MIM# 145900; Neuropathy, recurrent, with pressure palsies 162500; Roussy-Levy syndrome 180800
Genomic newborn screening: BabyScreen+ v0.1586 PMP22 Zornitza Stark Classified gene: PMP22 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1586 PMP22 Zornitza Stark Gene: pmp22 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1585 PMP22 Zornitza Stark reviewed gene: PMP22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 1A, MIM# 118220, Charcot-Marie-Tooth disease, type 1E, MIM# 118300, Dejerine-Sottas disease, MIM# 145900, Neuropathy, recurrent, with pressure palsies 162500, Roussy-Levy syndrome 180800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1585 PMM2 Zornitza Stark Gene: pmm2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1583 PMM2 Zornitza Stark Classified gene: PMM2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1583 PMM2 Zornitza Stark Gene: pmm2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1582 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1581 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1580 PLP1 Zornitza Stark Classified gene: PLP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1580 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1579 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1578 PLOD1 Zornitza Stark Classified gene: PLOD1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1578 PLOD1 Zornitza Stark Gene: plod1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1577 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1576 PLEC Zornitza Stark Gene: plec has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1576 PLEC Zornitza Stark Phenotypes for gene: PLEC were changed from Muscular dystrophy; Epidermolysis bullosa simplex to Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670; Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138; Epidermolysis bullosa simplex, Ogna type MIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723
Genomic newborn screening: BabyScreen+ v0.1574 PLEC Zornitza Stark Classified gene: PLEC as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1574 PLEC Zornitza Stark Gene: plec has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1573 PLEC Zornitza Stark reviewed gene: PLEC: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex with muscular dystrophy, MIM# 226670, Epidermolysis bullosa simplex with pyloric atresia, MIM# 612138, Epidermolysis bullosa simplex, Ogna type MIM#131950, Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM# 613723; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1573 PLCE1 Zornitza Stark Gene: plce1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1572 PLCE1 Zornitza Stark Classified gene: PLCE1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1572 PLCE1 Zornitza Stark Gene: plce1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1571 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1571 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
Genomic newborn screening: BabyScreen+ v0.1570 PLA2G6 Zornitza Stark Classified gene: PLA2G6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1570 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1569 PLA2G6 Zornitza Stark reviewed gene: PLA2G6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217, Parkinson disease 14, autosomal recessive MIM#612953; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1569 PKLR Zornitza Stark Gene: pklr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1568 PKLR Zornitza Stark changed review comment from: ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis.; to: Established gene-disease association.

Severity ranges from fetal hydrops and symptomatic anaemia requiring lifelong transfusions to fully compensated haemolysis.

Treatment: Mitapivat. Red cell transfusions.

For review.
Genomic newborn screening: BabyScreen+ v0.1568 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1567 PKHD1 Zornitza Stark Classified gene: PKHD1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1567 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1566 PKD2 Zornitza Stark Gene: pkd2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1565 PKD2 Zornitza Stark Classified gene: PKD2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1565 PKD2 Zornitza Stark Gene: pkd2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1564 PKD1 Zornitza Stark Gene: pkd1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1563 PKD1 Zornitza Stark Classified gene: PKD1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1563 PKD1 Zornitza Stark Gene: pkd1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1562 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1562 PIK3CA Zornitza Stark Classified gene: PIK3CA as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1562 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1561 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to gNBS. Sources: Expert list
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CA were set to 33392635; 33639990
Phenotypes for gene: PIK3CA were set to PIK3CA related overgrowth spectrum
Review for gene: PIK3CA was set to AMBER
Added comment: Established association with a range of overgrowth phenotypes.

Note variants are SOMATIC and may not be detectable reliably.

Treatment: alpelisib, miransertib. Unsure if these are available.
Sources: Expert list
Genomic newborn screening: BabyScreen+ v0.1560 PINK1 Zornitza Stark Gene: pink1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1558 PINK1 Zornitza Stark Classified gene: PINK1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1558 PINK1 Zornitza Stark Gene: pink1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1557 PIK3R1 Zornitza Stark Gene: pik3r1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1556 PIK3R1 Zornitza Stark reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31111319, 33401995, 34033842; Phenotypes: Immunodeficiency 36, MIM# 616005, Agammaglobulinemia 7, autosomal recessive , MIM# 615214; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1556 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1556 PIK3CD Zornitza Stark Phenotypes for gene: PIK3CD were changed from Immunodeficiency 14, MIM # 615513 to Immunodeficiency 14B, autosomal recessive, MIM# 619281; Immunodeficiency 14A, autosomal dominant, MIM# 615513
Genomic newborn screening: BabyScreen+ v0.1553 PIK3CD Zornitza Stark reviewed gene: PIK3CD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30040974, 30336224, 29180244, 16984281, 24136356, 24165795, 24610295; Phenotypes: Immunodeficiency 14B, autosomal recessive, MIM# 619281, Immunodeficiency 14A, autosomal dominant, MIM# 615513; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1553 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1553 PIEZO2 Zornitza Stark Phenotypes for gene: PIEZO2 were changed from Arthrogryposis, distal, type 5 to Marden-Walker syndrome (MIM#248700); Arthrogryposis, distal, type 3 (MIM#114300); Arthrogryposis, distal, type 5 (MIM#108145); Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146
Genomic newborn screening: BabyScreen+ v0.1551 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1551 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1550 PIEZO2 Zornitza Stark reviewed gene: PIEZO2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marden-Walker syndrome (MIM#248700), Arthrogryposis, distal, type 3 (MIM#114300), Arthrogryposis, distal, type 5 (MIM#108145), Arthrogryposis, distal, with impaired proprioception and touch, MIM# 617146; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1550 PDZD7 Zornitza Stark Gene: pdzd7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1550 PDZD7 Zornitza Stark Phenotypes for gene: PDZD7 were changed from Usher syndrome to Deafness, autosomal recessive 57, MIM# 618003; Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472
Genomic newborn screening: BabyScreen+ v0.1549 PDZD7 Zornitza Stark reviewed gene: PDZD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 57, MIM# 618003, Usher syndrome, type IIC, GPR98/PDZD7 digenic, MIM# 605472; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1549 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1548 PHF6 Zornitza Stark Classified gene: PHF6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1548 PHF6 Zornitza Stark Gene: phf6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1547 PHEX Zornitza Stark Gene: phex has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1545 PGM3 Zornitza Stark Gene: pgm3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1545 TCOF1 Seb Lunke Gene: tcof1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1544 TCOF1 Seb Lunke Classified gene: TCOF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1544 TCOF1 Seb Lunke Gene: tcof1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1543 TCN2 Seb Lunke Gene: tcn2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1542 TCIRG1 Seb Lunke Gene: tcirg1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1542 TCIRG1 Seb Lunke Phenotypes for gene: TCIRG1 were changed from Osteopetrosis, infantile malignant to Osteopetrosis, autosomal recessive 1, MIM# 259700
Genomic newborn screening: BabyScreen+ v0.1541 TCIRG1 Seb Lunke reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 1, MIM# 259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1541 TCF3 Seb Lunke Gene: tcf3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1541 TCF3 Seb Lunke Phenotypes for gene: TCF3 were changed from Agammaglobulinaemia 8, autosomal dominant, MIM# 616941 to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
Genomic newborn screening: BabyScreen+ v0.1539 TCF3 Seb Lunke reviewed gene: TCF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941, Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1539 TBX5 Seb Lunke Gene: tbx5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1538 TBX5 Seb Lunke Classified gene: TBX5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1538 TBX5 Seb Lunke Gene: tbx5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1537 TBX19 Seb Lunke Gene: tbx19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1536 TBX1 Seb Lunke Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1535 TBX1 Seb Lunke Classified gene: TBX1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1535 TBX1 Seb Lunke Gene: tbx1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1534 TBC1D24 Seb Lunke Gene: tbc1d24 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1533 TBC1D24 Seb Lunke Classified gene: TBC1D24 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1533 TBC1D24 Seb Lunke Gene: tbc1d24 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1532 TAZ Seb Lunke Gene: taz has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1531 TAZ Seb Lunke Classified gene: TAZ as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1531 TAZ Seb Lunke Gene: taz has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1530 SURF1 Seb Lunke Gene: surf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1529 SURF1 Seb Lunke Classified gene: SURF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1529 SURF1 Seb Lunke Gene: surf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1528 SUOX Seb Lunke Gene: suox has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1527 SUOX Seb Lunke Classified gene: SUOX as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1527 SUOX Seb Lunke Gene: suox has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1526 SUCLG1 Seb Lunke Gene: suclg1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1525 SUCLG1 Seb Lunke Classified gene: SUCLG1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1525 SUCLG1 Seb Lunke Gene: suclg1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1524 SUCLA2 Seb Lunke Gene: sucla2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1523 SUCLA2 Seb Lunke Classified gene: SUCLA2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1523 SUCLA2 Seb Lunke Gene: sucla2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1522 STXBP2 Seb Lunke Gene: stxbp2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1522 STXBP2 Seb Lunke Phenotypes for gene: STXBP2 were changed from Haemophagocytic lymphohistiocytosis, MIM#613101 to Hemophagocytic lymphohistiocytosis, familial, 5, MIM# 613101
Genomic newborn screening: BabyScreen+ v0.1521 STXBP2 Seb Lunke reviewed gene: STXBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 5, MIM# 613101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1521 STXBP1 Seb Lunke Gene: stxbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1520 STXBP1 Seb Lunke Classified gene: STXBP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1520 STXBP1 Seb Lunke Gene: stxbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1519 STX11 Seb Lunke Gene: stx11 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1519 STX11 Seb Lunke reviewed gene: STX11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophagocytic lymphohistiocytosis, familial, 4 , MIM#603552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1519 STS Seb Lunke Gene: sts has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1519 STS Seb Lunke Phenotypes for gene: STS were changed from Ichthyosis, X-linked to Ichthyosis, X-linked, MIM# 308100
Genomic newborn screening: BabyScreen+ v0.1518 STS Seb Lunke Classified gene: STS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1518 STS Seb Lunke Gene: sts has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1517 STS Seb Lunke reviewed gene: STS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, X-linked, MIM# 308100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1517 TMC1 Lilian Downie reviewed gene: TMC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:11850618, PMID: 26879195; Phenotypes: Deafness, autosomal recessive 7 MIM#600974; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1517 TMEM43 Lilian Downie reviewed gene: TMEM43: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301310, PMID: 34674311; Phenotypes: Arrhythmogenic right ventricular dysplasia 5 MIM#604400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1517 STRC Seb Lunke Gene: strc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1517 STRC Seb Lunke Phenotypes for gene: STRC were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 16, MIM# 603720
Genomic newborn screening: BabyScreen+ v0.1516 STRC Seb Lunke Classified gene: STRC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1516 STRC Seb Lunke Gene: strc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1515 STRC Seb Lunke reviewed gene: STRC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 16, MIM# 603720; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1515 STRA6 Seb Lunke Gene: stra6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1514 STRA6 Seb Lunke Classified gene: STRA6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1514 STRA6 Seb Lunke Gene: stra6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1513 STK11 Seb Lunke Gene: stk11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1511 STK11 Seb Lunke Classified gene: STK11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1511 STK11 Seb Lunke Gene: stk11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1510 STAT3 Seb Lunke Gene: stat3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1509 STAR Seb Lunke Gene: star has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1509 STAR Seb Lunke Phenotypes for gene: STAR were changed from Congenital lipoid adrenal hyperplasia, MIM#201710 to Congenital lipoid adrenal hyperplasia, MIM#201710
Genomic newborn screening: BabyScreen+ v0.1508 STAR Seb Lunke reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1508 STAC3 Seb Lunke Gene: stac3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1508 STAC3 Seb Lunke Classified gene: STAC3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1508 STAC3 Seb Lunke Gene: stac3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1507 SRP54 Seb Lunke Gene: srp54 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1507 SRCAP Seb Lunke Gene: srcap has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1506 SRCAP Seb Lunke Classified gene: SRCAP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1506 SRCAP Seb Lunke Gene: srcap has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1505 SPTLC1 Seb Lunke Gene: sptlc1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1504 SPTLC1 Seb Lunke Classified gene: SPTLC1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1504 SPTLC1 Seb Lunke Gene: sptlc1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1503 PRX Zornitza Stark Gene: prx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1502 PRX Zornitza Stark Classified gene: PRX as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1502 PRX Zornitza Stark Gene: prx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1501 PSAP Zornitza Stark Gene: psap has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1501 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Metachromatic leukodystrophy to Parkinson disease; Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; Gaucher disease, atypical, MIM# 610539
Genomic newborn screening: BabyScreen+ v0.1499 PSAP Zornitza Stark Classified gene: PSAP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1499 PSAP Zornitza Stark Gene: psap has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1498 PSAP Zornitza Stark reviewed gene: PSAP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson disease, Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, Gaucher disease, atypical, MIM# 610539; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1498 TMEM67 Lilian Downie reviewed gene: TMEM67: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20232449 PMID: 26092869, PMID: 27336129; Phenotypes: COACH syndrome MIM#216360, Joubert syndrome MIM#10688, Meckel syndrome MIM#607361, Nephronophthisis MIM#613550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1498 TMIE Lilian Downie reviewed gene: TMIE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301607, PMID: 33987950; Phenotypes: Deafness, autosomal recessive 6 MIM#600971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1498 TMPRSS3 Lilian Downie reviewed gene: TMPRSS3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34868270; Phenotypes: deafness, autosomal recessive MIM#601072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1498 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1497 PTCH1 Zornitza Stark Classified gene: PTCH1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1497 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1496 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1495 PTEN Zornitza Stark Classified gene: PTEN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1495 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1494 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1494 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1494 PTH1R Zornitza Stark Gene: pth1r has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1494 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from Metaphyseal chondrodysplasia to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
Genomic newborn screening: BabyScreen+ v0.1492 PTH1R Zornitza Stark Classified gene: PTH1R as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1492 PTH1R Zornitza Stark Gene: pth1r has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1491 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1491 PTPRC Zornitza Stark Gene: ptprc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1491 PTPRC Zornitza Stark reviewed gene: PTPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, T cell-negative, B-cell/natural killer-cell positive MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1491 PYGL Zornitza Stark Gene: pygl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1490 SPTB Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: no specific treatment available (?Are these treatable by HSCT?)

Non-genetic confirmatory test: not assessed; to: Established gene-disease association.

Childhood onset, haematological disorder. Elliptocytosis, aneamia in some cases

Treatment: no specific treatment available (?Are these treatable by HSCT?)

Non-genetic confirmatory test: not assessed
Genomic newborn screening: BabyScreen+ v0.1490 SPTB Seb Lunke Phenotypes for gene: SPTB were changed from Spherocytosis to Anaemia, neonatal haemolytic, fatal or near-fatal MIM# 617948
Genomic newborn screening: BabyScreen+ v0.1489 SPTB Seb Lunke Classified gene: SPTB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1489 SPTB Seb Lunke Gene: sptb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1488 SPTA1 Seb Lunke Gene: spta1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1488 SPTA1 Seb Lunke Phenotypes for gene: SPTA1 were changed from Elliptocytosis to Elliptocytosis-2 MIM# 130600; Pyropoikilocytosis MIM# 266140; Spherocytosis, type 3 MIM# 270970
Genomic newborn screening: BabyScreen+ v0.1486 SPTA1 Seb Lunke Classified gene: SPTA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1486 SPTA1 Seb Lunke Gene: spta1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1485 SPTA1 Seb Lunke reviewed gene: SPTA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Elliptocytosis-2 MIM# 130600, Pyropoikilocytosis MIM# 266140, Spherocytosis, type 3 MIM# 270970; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1485 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1483 PYGM Zornitza Stark Classified gene: PYGM as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1483 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1482 RASA1 Zornitza Stark Gene: rasa1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1481 RASA1 Zornitza Stark Classified gene: RASA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1481 RASA1 Zornitza Stark Gene: rasa1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1480 RB1 Zornitza Stark Gene: rb1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1479 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1478 RAG1 Zornitza Stark Gene: rag1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1478 RAG1 Zornitza Stark Phenotypes for gene: RAG1 were changed from Omenn syndrome, MIM#603554 to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457
Genomic newborn screening: BabyScreen+ v0.1477 RAG1 Zornitza Stark reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889, Combined cellular and humoral immune defects with granulomas MIM# 233650, Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1477 RAG2 Zornitza Stark Gene: rag2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1476 RAB7A Zornitza Stark Gene: rab7a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1475 RAB7A Zornitza Stark Classified gene: RAB7A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1475 RAB7A Zornitza Stark Gene: rab7a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1474 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1474 RAB3GAP2 Zornitza Stark Classified gene: RAB3GAP2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1474 RAB3GAP2 Zornitza Stark Gene: rab3gap2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1473 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1472 RAB3GAP1 Zornitza Stark Classified gene: RAB3GAP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1472 RAB3GAP1 Zornitza Stark Gene: rab3gap1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1471 RAB27A Zornitza Stark Gene: rab27a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1470 ORAI1 Zornitza Stark Gene: orai1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1470 ORAI1 Zornitza Stark Classified gene: ORAI1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1470 ORAI1 Zornitza Stark Gene: orai1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1469 ORAI1 Zornitza Stark gene: ORAI1 was added
gene: ORAI1 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: ORAI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ORAI1 were set to Immunodeficiency 9, MIM# 612782
Review for gene: ORAI1 was set to GREEN
Added comment: PMID 31448844 (comprehensive review, summarises all published cases, references functional evidence):
- Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM)
- Recessive ORAI1 variants via a LOF mechanism cause a combined immunodeficiency (recurrent and chronic infections, autoimmunity, ectodermal dysplasia, non-progressive myopathy)

Included here for AR disease. Onset is in newborn period. Life-threatening.

Treatment: BMT.

Non-genetic confirmatory testing: T cell proliferation assay
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1468 RAI1 Zornitza Stark Gene: rai1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1467 RAI1 Zornitza Stark Classified gene: RAI1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1467 RAI1 Zornitza Stark Gene: rai1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1466 RBM8A Zornitza Stark Gene: rbm8a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1465 RBM8A Zornitza Stark Classified gene: RBM8A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1465 RBM8A Zornitza Stark Gene: rbm8a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1464 RAB23 Zornitza Stark Gene: rab23 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1463 RAB23 Zornitza Stark Classified gene: RAB23 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1463 RAB23 Zornitza Stark Gene: rab23 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1462 RAF1 Zornitza Stark Gene: raf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1461 RAF1 Zornitza Stark Classified gene: RAF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1461 RAF1 Zornitza Stark Gene: raf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1460 RDX Zornitza Stark Gene: rdx has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1460 RDX Zornitza Stark reviewed gene: RDX: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 24, MIM# 611022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1460 RECQL4 Zornitza Stark Gene: recql4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1459 RECQL4 Zornitza Stark Classified gene: RECQL4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1459 RECQL4 Zornitza Stark Gene: recql4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1458 RET Zornitza Stark reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple endocrine neoplasia IIA, MIM# 171400, Multiple endocrine neoplasia IIB, MIM# 162300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1458 REN Zornitza Stark Gene: ren has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1458 REN Zornitza Stark Phenotypes for gene: REN were changed from Renal tubular dysgenesis to Renal tubular dysgenesis, MIM# 267430
Genomic newborn screening: BabyScreen+ v0.1456 REN Zornitza Stark changed review comment from: Established gene-disease association.

Presents as fetal anuria leading to perinatal death.

No specific treatment.; to: Established gene-disease association.

Bi-allelic LOF variants cause renal tubular dysgenesis, which presents as fetal anuria leading to perinatal death.. Mono-allelic variants, likely through a different mechanism (mostly missense) cause tubulointerstitial disease. More severe phenotype associated with variants that are located in the protein leader peptide and affecting its co-translational insertion in the endoplasmic reticulum (ER).

No specific treatment for either.
Genomic newborn screening: BabyScreen+ v0.1456 REN Zornitza Stark Classified gene: REN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1456 REN Zornitza Stark Gene: ren has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1455 REN Zornitza Stark reviewed gene: REN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1455 RETREG1 Zornitza Stark Gene: retreg1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1454 RETREG1 Zornitza Stark Classified gene: RETREG1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1454 RETREG1 Zornitza Stark Gene: retreg1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1453 RFWD3 Zornitza Stark Gene: rfwd3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1453 RFWD3 Zornitza Stark Classified gene: RFWD3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1453 RFWD3 Zornitza Stark Gene: rfwd3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1452 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1452 CIITA Zornitza Stark Classified gene: CIITA as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1452 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1451 CIITA Zornitza Stark gene: CIITA was added
gene: CIITA was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: CIITA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CIITA were set to Bare Lymphocyte Syndrome, type II, complementation group A MIM# 209920
Review for gene: CIITA was set to GREEN
Added comment: 13 individuals of 11 unrelated families; two mouse models. Homozygous and compound heterozygous variants were identified in these individuals (missense, nonsense and splicing) resulting in premature stop codon and truncated protein, or inactive protein. Affected individuals typically present in infancy with severe (recurrent) respiratory and gastrointestinal tract infections and defective MHC II expression in PBMCs

Treatment: BMT.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1450 RFXAP Zornitza Stark Gene: rfxap has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1450 RFXAP Zornitza Stark Classified gene: RFXAP as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1450 RFXAP Zornitza Stark Gene: rfxap has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1449 RFXAP Zornitza Stark gene: RFXAP was added
gene: RFXAP was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: RFXAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RFXAP were set to Bare lymphocyte syndrome, type II, complementation group D MIM# 209920
Review for gene: RFXAP was set to GREEN
Added comment: 9 unique RFXAP variants in 12 unrelated individuals have been reported; one mouse model

The most frequent variant is a deletion c. delG484fsX525 which has been identified in 4 individuals of different origins (North African, Turkish and East Asian).

Typically presents in infancy with recurrent bacterial infections, severe diarrhoea and failure to thrive.

Treatment: BMT.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1448 RFX5 Zornitza Stark Gene: rfx5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1448 RFX5 Zornitza Stark Classified gene: RFX5 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1448 RFX5 Zornitza Stark Gene: rfx5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1447 RFX5 Zornitza Stark gene: RFX5 was added
gene: RFX5 was added to gNBS. Sources: Expert Review
Mode of inheritance for gene: RFX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RFX5 were set to Bare lymphocyte syndrome, type II, complementation group C MIM# 209920; Bare lymphocyte syndrome, type II, complementation group E MIM# 209920
Review for gene: RFX5 was set to GREEN
Added comment: Bare lymphocyte syndrome, type II, complementation group C

9 individuals from 8 unrelated families; multiple mouse models
Homozygous and Compound heterozygous (Nonsense, missense, splice site, single bp del) variants were reported resulting in truncated protein and loss of function.
All individuals presented with recurrent lower respiratory tract infection early in life, low CD4+ cells and/or failure to thrive, chronic diarrhoea, hepatosplenomegaly and low Ig levels.
----------
Bare lymphocyte syndrome, type II, complementation group E

2 siblings (twins) reported with RPX5 variants and new BLS group E phenotype; multiple functional studies
Identified homozygous missense variant (R149Q) which resulted in altered DNA-binding domain and loss of function.
These histo-identical twin brothers had normal numbers of CD4 + cells and are able to mount both cellular and humoral immune responses. They displayed absence of MHC class II surface expression on B cells and mononuclear cells.

Presentation is typically in infancy.

Treatment: BMT.
Sources: Expert Review
Genomic newborn screening: BabyScreen+ v0.1446 RFXANK Zornitza Stark Gene: rfxank has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1446 RMRP Zornitza Stark Gene: rmrp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1446 RMRP Zornitza Stark Phenotypes for gene: RMRP were changed from Cartilage-hair hypoplasia to Cartilage-hair hypoplasia MIM#250250
Genomic newborn screening: BabyScreen+ v0.1445 RMRP Zornitza Stark reviewed gene: RMRP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cartilage-hair hypoplasia MIM#250250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1445 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1444 RNASEH2A Zornitza Stark Classified gene: RNASEH2A as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1444 RNASEH2A Zornitza Stark Gene: rnaseh2a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1443 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1441 RNASEH2B Zornitza Stark Classified gene: RNASEH2B as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1441 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1440 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1438 RNASEH2C Zornitza Stark Classified gene: RNASEH2C as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1438 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1437 ROR2 Zornitza Stark Gene: ror2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1437 ROR2 Zornitza Stark Phenotypes for gene: ROR2 were changed from Robinow syndrome; Brachydactyly, type B1 to Robinow syndrome, autosomal recessive - MIM#268310
Genomic newborn screening: BabyScreen+ v0.1435 ROR2 Zornitza Stark Classified gene: ROR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1435 ROR2 Zornitza Stark Gene: ror2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1434 ROR2 Zornitza Stark reviewed gene: ROR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Robinow syndrome, autosomal recessive - MIM#268310; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1434 RPGR Zornitza Stark Gene: rpgr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1434 RPGR Zornitza Stark Phenotypes for gene: RPGR were changed from Retinitis pigmentosa to Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455
Genomic newborn screening: BabyScreen+ v0.1433 RPGR Zornitza Stark Classified gene: RPGR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1433 RPGR Zornitza Stark Gene: rpgr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1432 RPGR Zornitza Stark reviewed gene: RPGR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness, MIM# 300455; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1432 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1432 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from Joubert syndrome; Meckel syndrome to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Nephronophthisis
Genomic newborn screening: BabyScreen+ v0.1431 RPGRIP1L Zornitza Stark Classified gene: RPGRIP1L as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1431 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1430 RPGRIP1L Zornitza Stark reviewed gene: RPGRIP1L: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 7, MIM# 611560, Meckel syndrome 5, MIM# 611561, COACH syndrome 3, MIM# 619113, Nephronophthisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1430 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1430 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1430 RPL18 Zornitza Stark Gene: rpl18 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1430 RPL18 Zornitza Stark Classified gene: RPL18 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1430 RPL18 Zornitza Stark Gene: rpl18 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1429 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1429 RPL26 Zornitza Stark Classified gene: RPL26 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1429 RPL26 Zornitza Stark Gene: rpl26 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1428 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1428 RPL27 Zornitza Stark Classified gene: RPL27 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1428 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1427 RPL35 Zornitza Stark Gene: rpl35 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1427 RPL35 Zornitza Stark Classified gene: RPL35 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1427 RPL35 Zornitza Stark Gene: rpl35 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1426 RPL5 Zornitza Stark Gene: rpl5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1426 KARS Zornitza Stark Classified gene: KARS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1426 KARS Zornitza Stark Gene: kars has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1425 KARS Zornitza Stark changed review comment from: Variants in this gene are associated with either isolated or complex deafness with leukoencephalopathy.

The deafness tends to be congenital/pre-lingual. For review, likely meets criteria though some individuals will have leukoencephalopathy which does not have a specific treatment.; to: Variants in this gene are associated with either isolated or complex deafness with leukoencephalopathy.

The deafness tends to be congenital/pre-lingual. For review, likely meets criteria though some individuals will have leukoencephalopathy which does not have a specific treatment.

Reviewed: significant uncertainty regarding outcome, exclude.
Genomic newborn screening: BabyScreen+ v0.1425 RYR1 Zornitza Stark changed review comment from: Well established association with susceptibility to malignant hyperthermia.

However, variants in this gene also cause a range of muscular phenotypes, for which there is no specific treatment.

Association with malignant hyperthermia is rated 'strongly actionable' in children by ClinGen.

MH susceptibility (MHS) is a pharmacogenetic skeletal muscle disorder where exposure to certain volatile anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, sevoflurane), either alone or with a depolarizing muscle relaxant (succinylcholine), may trigger uncontrolled skeletal muscle hypermetabolism. An MH episode may begin with hypercapnia, rapidly rising end-tidal CO2, and tachycardia followed by hyperthermia. Additional symptoms may include acidosis, muscle rigidity, compartment syndrome, rhabdomyolysis and subsequent increased creatine kinase, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure.

There is mounting evidence that some individuals with MHS may also develop episodes triggered by non-anesthetic conditions such as heat and/or exercise. These non-anesthetic-induced episodes, often called MH-like syndrome, may manifest as exertional rhabdomyolysis (ER).

Surgical management recommendations include preparation of the anesthesia workstation to reduce or prevent exposure to triggering anesthetics (e.g., remove vaporizers from machine and replace all disposables), vigilant monitoring for signs and symptoms of MH during perioperative period, and close observation and monitoring postoperatively.

MHS patients should carry identification of their susceptibility and inform those responsible for their care of their MH status.

Do not use the following MH triggering drugs for MHS patients: inhaled general anesthetics (desflurane, enflurane, halothane, isoflurane, sevoflurane) and depolarizing muscle relaxants (succinylcholine).

For review.; to: Well established association with susceptibility to malignant hyperthermia.

However, variants in this gene also cause a range of muscular phenotypes, for which there is no specific treatment.

Association with malignant hyperthermia is rated 'strongly actionable' in children by ClinGen.

MH susceptibility (MHS) is a pharmacogenetic skeletal muscle disorder where exposure to certain volatile anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, sevoflurane), either alone or with a depolarizing muscle relaxant (succinylcholine), may trigger uncontrolled skeletal muscle hypermetabolism. An MH episode may begin with hypercapnia, rapidly rising end-tidal CO2, and tachycardia followed by hyperthermia. Additional symptoms may include acidosis, muscle rigidity, compartment syndrome, rhabdomyolysis and subsequent increased creatine kinase, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure.

There is mounting evidence that some individuals with MHS may also develop episodes triggered by non-anesthetic conditions such as heat and/or exercise. These non-anesthetic-induced episodes, often called MH-like syndrome, may manifest as exertional rhabdomyolysis (ER).

Surgical management recommendations include preparation of the anesthesia workstation to reduce or prevent exposure to triggering anesthetics (e.g., remove vaporizers from machine and replace all disposables), vigilant monitoring for signs and symptoms of MH during perioperative period, and close observation and monitoring postoperatively.

MHS patients should carry identification of their susceptibility and inform those responsible for their care of their MH status.

Do not use the following MH triggering drugs for MHS patients: inhaled general anesthetics (desflurane, enflurane, halothane, isoflurane, sevoflurane) and depolarizing muscle relaxants (succinylcholine).
Genomic newborn screening: BabyScreen+ v0.1425 DMD Zornitza Stark changed review comment from: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only.

Onset in early childhood.

Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping.

Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels.

For review.; to: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only.

Onset in early childhood.

Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping.

Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels.

For review. Discuss with neurology. Should we only report variants that are likely to benefit from treatment?
Genomic newborn screening: BabyScreen+ v0.1425 SPRED1 Seb Lunke Gene: spred1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1424 SPRED1 Seb Lunke Classified gene: SPRED1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1424 SPRED1 Seb Lunke Gene: spred1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1423 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1421 DMD Zornitza Stark Classified gene: DMD as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1421 DMD Zornitza Stark Gene: dmd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1420 SLC39A7 Zornitza Stark reviewed gene: SLC39A7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Agammaglobulinaemia 9, autosomal recessive, MIM# 619693; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1420 SPR Seb Lunke Gene: spr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1420 SPR Seb Lunke Phenotypes for gene: SPR were changed from Sepiapterin reductase deficiency to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Genomic newborn screening: BabyScreen+ v0.1419 SPR Seb Lunke reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1418 SPINK5 Seb Lunke Gene: spink5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1417 SPINK5 Seb Lunke Classified gene: SPINK5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1417 SPINK5 Seb Lunke Gene: spink5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1416 SPEG Seb Lunke Gene: speg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1416 SPEG Seb Lunke Classified gene: SPEG as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1416 SPEG Seb Lunke Gene: speg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1415 SP110 Seb Lunke Gene: sp110 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1415 SP110 Seb Lunke Phenotypes for gene: SP110 were changed from Hepatic venoocclusive disease with immunodeficiency to Hepatic veno-occlusive disease with immunodeficiency MIM#235550
Genomic newborn screening: BabyScreen+ v0.1414 SP110 Seb Lunke reviewed gene: SP110: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatic veno-occlusive disease with immunodeficiency MIM#235550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1414 SOX9 Seb Lunke Gene: sox9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1414 SOX9 Seb Lunke Phenotypes for gene: SOX9 were changed from Campomelic dysplasia to Campomelic dysplasia, MIM# 114290
Genomic newborn screening: BabyScreen+ v0.1413 SOX9 Seb Lunke Classified gene: SOX9 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1413 SOX9 Seb Lunke Gene: sox9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1412 SOX9 Seb Lunke reviewed gene: SOX9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1412 SOX10 Seb Lunke Gene: sox10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1412 SOX10 Seb Lunke Classified gene: SOX10 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1412 SOX10 Seb Lunke Gene: sox10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1411 SNAP25 Seb Lunke Gene: snap25 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1409 SNAP25 Seb Lunke Classified gene: SNAP25 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1409 SNAP25 Seb Lunke Gene: snap25 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1408 SMPX Seb Lunke Gene: smpx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1407 SMPX Seb Lunke Classified gene: SMPX as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1407 SMPX Seb Lunke Gene: smpx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1406 SMPD1 Seb Lunke Gene: smpd1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1404 SMC1A Seb Lunke Gene: smc1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1402 SMC1A Seb Lunke Classified gene: SMC1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1402 SMC1A Seb Lunke Gene: smc1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1400 RPS15 Zornitza Stark Gene: rps15 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1398 RPS15 Zornitza Stark Classified gene: RPS15 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1398 RPS15 Zornitza Stark Gene: rps15 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1397 RPS15 Zornitza Stark changed review comment from: Single individual reported.; to: Single individual reported in 2008, no reports since.
Genomic newborn screening: BabyScreen+ v0.1397 RPS15A Zornitza Stark Gene: rps15a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1397 RPS15A Zornitza Stark Classified gene: RPS15A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1397 RPS15A Zornitza Stark Gene: rps15a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 RPS17 Zornitza Stark Gene: rps17 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 RPS19 Zornitza Stark Gene: rps19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 RPS24 Zornitza Stark Gene: rps24 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 RPS26 Zornitza Stark Gene: rps26 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 SMARCAL1 Seb Lunke Gene: smarcal1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1396 SMARCAL1 Seb Lunke Phenotypes for gene: SMARCAL1 were changed from Schimke immunoosseous dysplasia to Schimke immune-osseous dysplasia MIM# 242900
Genomic newborn screening: BabyScreen+ v0.1395 SMARCAL1 Seb Lunke Classified gene: SMARCAL1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1395 SMARCAL1 Seb Lunke Gene: smarcal1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1394 SMARCAL1 Seb Lunke reviewed gene: SMARCAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Schimke immune-osseous dysplasia MIM# 242900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1394 SMAD4 Seb Lunke Gene: smad4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1394 SMAD4 Seb Lunke Phenotypes for gene: SMAD4 were changed from Juvenile polyposis syndrome to Polyposis, juvenile intestinal, MIM# 174900; Myhre syndrome, MIM# 139210
Genomic newborn screening: BabyScreen+ v0.1392 SMAD4 Seb Lunke Classified gene: SMAD4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1392 SMAD4 Seb Lunke Gene: smad4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1391 SMAD4 Seb Lunke reviewed gene: SMAD4: Rating: RED; Mode of pathogenicity: None; Publications: 20301642; Phenotypes: Polyposis, juvenile intestinal, MIM# 174900, Myhre syndrome, MIM# 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1391 SMAD3 Seb Lunke Gene: smad3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1389 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1388 SLC6A8 Zornitza Stark Classified gene: SLC6A8 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1388 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1386 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1386 RPS27 Zornitza Stark Classified gene: RPS27 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1386 RPS27 Zornitza Stark Gene: rps27 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1385 RPS28 Zornitza Stark Gene: rps28 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1385 RPS28 Zornitza Stark Classified gene: RPS28 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1385 RPS28 Zornitza Stark Gene: rps28 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1384 RPS28 Zornitza Stark changed review comment from: Congenital onset.

DBA is a treatable disorder: corticosteroids, red blood cell transfusion, BMT.; to: Two individuals reported in 2014, none since.

Congenital onset.

DBA is a treatable disorder: corticosteroids, red blood cell transfusion, BMT.
Genomic newborn screening: BabyScreen+ v0.1384 RPS28 Zornitza Stark edited their review of gene: RPS28: Changed rating: RED; Changed phenotypes: Diamond Blackfan anemia 15 with mandibulofacial dysostosis, MIM# 606164; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1384 RPS29 Zornitza Stark Gene: rps29 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1384 RPS29 Zornitza Stark Classified gene: RPS29 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1384 RPS29 Zornitza Stark Gene: rps29 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1383 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1382 RPS6KA3 Zornitza Stark Classified gene: RPS6KA3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1382 RPS6KA3 Zornitza Stark Gene: rps6ka3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1381 RRM2B Zornitza Stark Gene: rrm2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1380 RRM2B Zornitza Stark Classified gene: RRM2B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1380 RRM2B Zornitza Stark Gene: rrm2b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1379 RS1 Zornitza Stark Gene: rs1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1379 RS1 Zornitza Stark Phenotypes for gene: RS1 were changed from Retinoschisis, X linked to Retinoschisis, MIM#312700
Genomic newborn screening: BabyScreen+ v0.1378 RS1 Zornitza Stark Classified gene: RS1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1378 RS1 Zornitza Stark Gene: rs1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1377 RS1 Zornitza Stark reviewed gene: RS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinoschisis, MIM#312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1377 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1377 RSPH4A Zornitza Stark Phenotypes for gene: RSPH4A were changed from Ciliary dyskinesia, primary to Ciliary dyskinesia, primary, 11 (MIM#612649)
Genomic newborn screening: BabyScreen+ v0.1376 RSPH4A Zornitza Stark Classified gene: RSPH4A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1376 RSPH4A Zornitza Stark Gene: rsph4a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1375 RSPH4A Zornitza Stark reviewed gene: RSPH4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 11 (MIM#612649); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1375 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1375 RSPH9 Zornitza Stark Phenotypes for gene: RSPH9 were changed from Ciliary dyskinesia, primary to Ciliary dyskinesia, primary, 12 (MIM#612650)
Genomic newborn screening: BabyScreen+ v0.1374 RSPH9 Zornitza Stark Classified gene: RSPH9 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1374 RSPH9 Zornitza Stark Gene: rsph9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1373 RSPH9 Zornitza Stark reviewed gene: RSPH9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 12 (MIM#612650); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1373 RUNX2 Zornitza Stark Gene: runx2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1373 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from Cleidocranial dysostosis to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510
Genomic newborn screening: BabyScreen+ v0.1372 RUNX2 Zornitza Stark Classified gene: RUNX2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1372 RUNX2 Zornitza Stark Gene: runx2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1371 RUNX2 Zornitza Stark reviewed gene: RUNX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1371 CACNA1S Zornitza Stark Gene: cacna1s has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1370 CACNA1S Zornitza Stark Classified gene: CACNA1S as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1370 CACNA1S Zornitza Stark Gene: cacna1s has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1369 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1367 RYR2 Zornitza Stark Gene: ryr2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1367 INSR Zornitza Stark Gene: insr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1365 INSR Zornitza Stark Classified gene: INSR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1365 INSR Zornitza Stark Gene: insr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1364 SLX4 Seb Lunke Gene: slx4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1364 SLCO2A1 Seb Lunke Gene: slco2a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1364 SLCO2A1 Seb Lunke Classified gene: SLCO2A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1364 SLCO2A1 Seb Lunke Gene: slco2a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1363 SLCO2A1 Seb Lunke reviewed gene: SLCO2A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1363 SLC9A6 Seb Lunke Gene: slc9a6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1362 SLC9A6 Seb Lunke Classified gene: SLC9A6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1362 SLC9A6 Seb Lunke Gene: slc9a6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1361 SLC7A9 Seb Lunke Gene: slc7a9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1360 SLC7A9 Seb Lunke Classified gene: SLC7A9 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1360 SLC7A9 Seb Lunke Gene: slc7a9 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1359 SLC7A7 Seb Lunke edited their review of gene: SLC7A7: Added comment: Established gene-disease association.

Childhood onset, multi-system disorder

Treatment: protein restriction, carnitine, citrulline, lysine supplementation, sodium benzoate

Non-genetic confirmatory test: 24-hour urinary excretion of cationic amino acids; Changed publications: 20301535
Genomic newborn screening: BabyScreen+ v0.1359 SLC7A7 Seb Lunke Gene: slc7a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1358 SLC7A7 Seb Lunke Phenotypes for gene: SLC7A7 were changed from Lysinuric protein intolerance to Lysinuric protein intolerance, MIM# 222700
Genomic newborn screening: BabyScreen+ v0.1357 SLC7A7 Seb Lunke reviewed gene: SLC7A7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lysinuric protein intolerance, MIM# 222700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1356 SLC6A8 Seb Lunke Classified gene: SLC6A8 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1356 SLC6A8 Seb Lunke Gene: slc6a8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1355 SLC6A5 Seb Lunke Gene: slc6a5 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1355 SLC6A5 Seb Lunke Classified gene: SLC6A5 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1355 SLC6A5 Seb Lunke Gene: slc6a5 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1354 SLC6A19 Seb Lunke Gene: slc6a19 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1354 SLC6A19 Seb Lunke Classified gene: SLC6A19 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1354 SLC6A19 Seb Lunke Gene: slc6a19 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1353 SLC5A5 Seb Lunke Gene: slc5a5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1353 SLC5A5 Seb Lunke Phenotypes for gene: SLC5A5 were changed from Thyroid dyshormonogenesis 1 to Thyroid dyshormonogenesis 1, MIM# 274400
Genomic newborn screening: BabyScreen+ v0.1351 SLC5A5 Seb Lunke reviewed gene: SLC5A5: Rating: ; Mode of pathogenicity: None; Publications: 33272083; Phenotypes: Thyroid dyshormonogenesis 1, MIM# 274400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1351 SLC5A1 Seb Lunke Gene: slc5a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1351 SLC52A3 Seb Lunke Gene: slc52a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1350 SLC52A2 Seb Lunke Gene: slc52a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1350 SLC4A11 Seb Lunke Gene: slc4a11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1348 SLC4A11 Seb Lunke Classified gene: SLC4A11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1348 SLC4A11 Seb Lunke Gene: slc4a11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1347 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1345 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1345 HBB Zornitza Stark Phenotypes for gene: HBB were changed from Beta-thalassemia to Sickle cell anaemia, MIM# 603903; Thalassaemia, beta, MIM# 613985
Genomic newborn screening: BabyScreen+ v0.1344 HBB Zornitza Stark reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sickle cell anaemia, MIM# 603903, Thalassaemia, beta, MIM# 613985; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1344 HBA2 Zornitza Stark Gene: hba2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1344 HBA1 Zornitza Stark Gene: hba1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1344 SLC4A1 Seb Lunke Gene: slc4a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1344 SLC4A1 Seb Lunke Phenotypes for gene: SLC4A1 were changed from Spherocytosis to Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590
Genomic newborn screening: BabyScreen+ v0.1341 SLC4A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, metabolic condition

Treatment: oral alkali replacement therapy, potassium chloride

Non-genetic confirmatory test: serum bicarbonate, chloride, potassium, urinary pH and anion gap; to: Established gene-disease association.

Childhood onset, metabolic condition

Treatment: oral alkali replacement therapy, potassium chloride. Not clear if treatment equally applicable to dominant and recessive forms of disease

Non-genetic confirmatory test: serum bicarbonate, chloride, potassium, urinary pH and anion gap
Genomic newborn screening: BabyScreen+ v0.1341 SLC4A1 Seb Lunke reviewed gene: SLC4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31600044; Phenotypes: Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1341 SLC46A1 Seb Lunke Gene: slc46a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1340 SLC46A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset, metabolic disorders

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels; to: Established gene-disease association.

Childhood onset, metabolic disorder

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels
Genomic newborn screening: BabyScreen+ v0.1340 SLC46A1 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset,

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels; to: Established gene-disease association.

Childhood onset, metabolic disorders

Treatment: 5-formyltetrahydrofolate (5-formylTHF, folinic acid, Leucovorin) or the active isomer of 5-formylTHF (Isovorin or Fusilev) Parenteral (intramuscular) or high-dose oral

Non-genetic confirmatory test: CSF and serum folate levels
Genomic newborn screening: BabyScreen+ v0.1340 SLC45A2 Seb Lunke Gene: slc45a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1339 SLC45A2 Seb Lunke Classified gene: SLC45A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1339 SLC45A2 Seb Lunke Gene: slc45a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1338 SLC3A1 Seb Lunke Gene: slc3a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1337 SLC3A1 Seb Lunke Classified gene: SLC3A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1337 SLC3A1 Seb Lunke Gene: slc3a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1336 SLC39A8 Seb Lunke Gene: slc39a8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1335 SLC39A4 Seb Lunke Gene: slc39a4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1333 SLC37A4 Seb Lunke Gene: slc37a4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1331 SLC37A4 Seb Lunke edited their review of gene: SLC37A4: Added comment: Established gene-disease association.

Childhood onset, metabolic disorder

Treatment: corn starch, nighttime intragastric continuous glucose infusion, allopurinol, statin, granulocyte-colony stimulating factor (G-CSF), empagliflozin

Non-genetic confirmatory test: no; Changed phenotypes: Glycogen storage disease Ib, MIM# 232220, Glycogen storage disease Ic, MIM# 232240, Congenital disorder of glycosylation, type IIw, MIM# 619525
Genomic newborn screening: BabyScreen+ v0.1331 SLC35D1 Seb Lunke Gene: slc35d1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1331 SLC35D1 Seb Lunke Phenotypes for gene: SLC35D1 were changed from Schneckenbecken dysplasia to Schneckenbecken dysplasia 269250, MONDO:0010013
Genomic newborn screening: BabyScreen+ v0.1330 SLC35D1 Seb Lunke Classified gene: SLC35D1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1330 SLC35D1 Seb Lunke Gene: slc35d1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1329 SLC35D1 Seb Lunke reviewed gene: SLC35D1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Schneckenbecken dysplasia 269250, MONDO:0010013; Mode of inheritance: None
Genomic newborn screening: BabyScreen+ v0.1329 SLC34A2 Seb Lunke Gene: slc34a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1329 SLC34A2 Seb Lunke Phenotypes for gene: SLC34A2 were changed from Pulmonary alveolar microlithiasis to Pulmonary alveolar microlithiasis, MIM# 265100
Genomic newborn screening: BabyScreen+ v0.1328 SLC34A2 Seb Lunke Classified gene: SLC34A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1328 SLC34A2 Seb Lunke Gene: slc34a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1327 SLC34A2 Seb Lunke reviewed gene: SLC34A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pulmonary alveolar microlithiasis, MIM# 265100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1327 SLC2A10 Seb Lunke Gene: slc2a10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1327 SLC2A10 Seb Lunke Phenotypes for gene: SLC2A10 were changed from Arterial tortuosity syndrome to Arterial tortuosity syndrome MIM#208050
Genomic newborn screening: BabyScreen+ v0.1326 SLC2A10 Seb Lunke Classified gene: SLC2A10 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1326 SLC2A10 Seb Lunke Gene: slc2a10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1325 SLC2A10 Seb Lunke reviewed gene: SLC2A10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial tortuosity syndrome MIM#208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1325 SLC2A1 Seb Lunke Gene: slc2a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1323 SLC27A4 Seb Lunke Gene: slc27a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1323 SLC27A4 Seb Lunke Phenotypes for gene: SLC27A4 were changed from Ichthyosis prematurity syndrome to Ichthyosis prematurity syndrome, MIM#608649
Genomic newborn screening: BabyScreen+ v0.1321 SLC27A4 Seb Lunke Classified gene: SLC27A4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1321 SLC27A4 Seb Lunke Gene: slc27a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1320 SLC27A4 Seb Lunke reviewed gene: SLC27A4: Rating: RED; Mode of pathogenicity: None; Publications: 20301593; Phenotypes: Ichthyosis prematurity syndrome, MIM#608649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1320 SLC26A4 Seb Lunke Gene: slc26a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1318 SLC26A4 Seb Lunke Classified gene: SLC26A4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1318 SLC26A4 Seb Lunke Gene: slc26a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1317 SLC39A7 Seb Lunke Gene: slc39a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1317 SLC39A7 Seb Lunke Classified gene: SLC39A7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1317 SLC39A7 Seb Lunke Gene: slc39a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1316 SLC39A7 Seb Lunke gene: SLC39A7 was added
gene: SLC39A7 was added to gNBS. Sources: Literature
Mode of inheritance for gene: SLC39A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A7 were set to 30718914
Phenotypes for gene: SLC39A7 were set to Agammaglobulinaemia 9, autosomal recessive, MIM# 619693
Added comment: Established gene-disease association.

Childhood onset, primary immunodeficiency

Treatment: Bone marrow transplant (hematopoietic stem cell transplantation (HSCT)), replacement immunoglobulin treatment

Non-genetic confirmatory test: immunoglobulin levels, T and B Lymphocyte and Natural Killer Cell Profile
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.1315 SLC35C1 Seb Lunke Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1313 SLC35C1 Seb Lunke Classified gene: SLC35C1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1313 SLC35C1 Seb Lunke Gene: slc35c1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1312 SLC35A2 Seb Lunke Gene: slc35a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1310 SLC35A2 Seb Lunke Classified gene: SLC35A2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1310 SLC35A2 Seb Lunke Gene: slc35a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1309 SLC30A10 Seb Lunke Gene: slc30a10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1309 SLC30A10 Seb Lunke Classified gene: SLC30A10 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1309 SLC30A10 Seb Lunke Gene: slc30a10 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1307 SLC39A14 Seb Lunke Gene: slc39a14 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1307 SLC39A14 Seb Lunke Classified gene: SLC39A14 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1307 SLC39A14 Seb Lunke Gene: slc39a14 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1305 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1303 GGCX Zornitza Stark Gene: ggcx has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1302 GNPTG Zornitza Stark Gene: gnptg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1302 GNPTG Zornitza Stark Phenotypes for gene: GNPTG were changed from Mucolipidosis III gamma to Mucolipidosis III gamma, MIM# 252605
Genomic newborn screening: BabyScreen+ v0.1300 GNPTG Zornitza Stark Classified gene: GNPTG as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1300 GNPTG Zornitza Stark Gene: gnptg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1299 GNPTG Zornitza Stark reviewed gene: GNPTG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucolipidosis III gamma, MIM# 252605; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1299 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1298 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1296 HCFC1 Zornitza Stark Classified gene: HCFC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1296 HCFC1 Zornitza Stark Gene: hcfc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1295 HNF1A Zornitza Stark Gene: hnf1a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1295 HNF1A Zornitza Stark Classified gene: HNF1A as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1295 HNF1A Zornitza Stark Gene: hnf1a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1294 HNF4A Zornitza Stark Gene: hnf4a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1293 HNF4A Zornitza Stark Classified gene: HNF4A as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1293 HNF4A Zornitza Stark Gene: hnf4a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1292 HOMER2 Zornitza Stark Gene: homer2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1291 HOMER2 Zornitza Stark Classified gene: HOMER2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1291 HOMER2 Zornitza Stark Gene: homer2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1290 HPS1 Zornitza Stark Gene: hps1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1289 HPS1 Zornitza Stark Classified gene: HPS1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1289 HPS1 Zornitza Stark Gene: hps1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1288 HPS3 Zornitza Stark Gene: hps3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1287 HPS3 Zornitza Stark Classified gene: HPS3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1287 HPS3 Zornitza Stark Gene: hps3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1286 HPS4 Zornitza Stark Gene: hps4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1285 HPS4 Zornitza Stark Classified gene: HPS4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1285 HPS4 Zornitza Stark Gene: hps4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1284 HPS5 Zornitza Stark Gene: hps5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1283 HPS5 Zornitza Stark Classified gene: HPS5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1283 HPS5 Zornitza Stark Gene: hps5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1282 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1282 PIGA Zornitza Stark Classified gene: PIGA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1282 PIGA Zornitza Stark Gene: piga has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1281 PIGA Zornitza Stark reviewed gene: PIGA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1281 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1279 HSD17B10 Zornitza Stark Classified gene: HSD17B10 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1279 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1278 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1276 HPRT1 Zornitza Stark Classified gene: HPRT1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1276 HPRT1 Zornitza Stark Gene: hprt1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1275 HGD Zornitza Stark Gene: hgd has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1273 HGD Zornitza Stark Classified gene: HGD as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1273 HGD Zornitza Stark Gene: hgd has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1272 IDUA John Christodoulou reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30143438; Phenotypes: coarse facie, corneal clouding, progressive neurodegeneration, dysostosis multiplex, hepatosplenomegaly, hernias, macrocephaly, cardiac valve involvement, SNHL, upper airways obstruction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1272 IDS John Christodoulou reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30143438, PMID: 33004112; Phenotypes: coarse facial features, cardiac valve involvement, hepatosplenomegaly, cardiomyopathy, airway obstruction, hydrocephalus, SNHL, dysostosis multiplex, kyphoscoliosis, progressive cognitive decline; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.1272 HSD17B10 John Christodoulou reviewed gene: HSD17B10: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 22127393; Phenotypes: cardiomyopathy, early-onset intractable seizures, progressive choreoathetosis, spastic tetraplegia, optic atrophy, retinal degeneration, intellectual disability; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.1272 HPRT1 John Christodoulou reviewed gene: HPRT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 18067674; Phenotypes: kidney stones, nephrocalcinosis, gout, dystonia, choreoathetosis, ballismus, cognitive impairment, self-injurious behaviour, megaloblastic anaemia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.1272 HGD John Christodoulou reviewed gene: HGD: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34344451, PMID: 12501223, PMID: 12501223; Phenotypes: progressive arthritis, progressive calcific cardiac valve damage, renal stones; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1272 HSD17B3 Zornitza Stark Gene: hsd17b3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1271 HSD17B3 Zornitza Stark Classified gene: HSD17B3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1271 HSD17B3 Zornitza Stark Gene: hsd17b3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1270 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1269 HSD17B4 Zornitza Stark Classified gene: HSD17B4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1269 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1268 HSD3B2 Zornitza Stark Gene: hsd3b2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1268 HSD3B2 Zornitza Stark reviewed gene: HSD3B2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency, MIM# 201810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1268 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1268 HSD3B7 Zornitza Stark Phenotypes for gene: HSD3B7 were changed from 3 beta-hydroxysteroid dehydrogenase deficiency to Bile acid synthesis defect, congenital, 1 MIM#607765
Genomic newborn screening: BabyScreen+ v0.1267 HSD3B7 Zornitza Stark reviewed gene: HSD3B7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30373615; Phenotypes: Bile acid synthesis defect, congenital, 1 MIM#607765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1267 HSPB8 Zornitza Stark Gene: hspb8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1266 HSPB8 Zornitza Stark Classified gene: HSPB8 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1266 HSPB8 Zornitza Stark Gene: hspb8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1265 HSPG2 Zornitza Stark Gene: hspg2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1265 HSPG2 Zornitza Stark Phenotypes for gene: HSPG2 were changed from Schwartz-Jampel syndrome to Schwartz-Jampel syndrome, type 1, MIM# 255800; MONDO:0009717; Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410; MONDO:0009140
Genomic newborn screening: BabyScreen+ v0.1264 HSPG2 Zornitza Stark Classified gene: HSPG2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1264 HSPG2 Zornitza Stark Gene: hspg2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1263 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, MONDO:0009717, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410, MONDO:0009140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1263 HTRA1 Zornitza Stark Gene: htra1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1263 HTRA1 Zornitza Stark Phenotypes for gene: HTRA1 were changed from CARASIL syndrome to CARASIL syndrome, MIM# 600142
Genomic newborn screening: BabyScreen+ v0.1262 HTRA1 Zornitza Stark Classified gene: HTRA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1262 HTRA1 Zornitza Stark Gene: htra1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1261 HTRA1 Zornitza Stark reviewed gene: HTRA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CARASIL syndrome, MIM# 600142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1261 SLC4A4 Seb Lunke Gene: slc4a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1261 SLC4A4 Seb Lunke Phenotypes for gene: SLC4A4 were changed from Renal tubular acidosis, proximal, with ocular abnormalities to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278
Genomic newborn screening: BabyScreen+ v0.1260 SLC4A4 Seb Lunke reviewed gene: SLC4A4: Rating: RED; Mode of pathogenicity: None; Publications: 24978391; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1260 ILDR1 Zornitza Stark Gene: ildr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1260 ILDR1 Zornitza Stark Phenotypes for gene: ILDR1 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 42, MIM# 609646
Genomic newborn screening: BabyScreen+ v0.1259 ILDR1 Zornitza Stark reviewed gene: ILDR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 42, MIM# 609646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1259 IL2RB Zornitza Stark Gene: il2rb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1259 SLC5A6 Seb Lunke Gene: slc5a6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1259 SLC5A6 Seb Lunke Phenotypes for gene: SLC5A6 were changed from to Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Genomic newborn screening: BabyScreen+ v0.1258 SLC5A6 Seb Lunke Classified gene: SLC5A6 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1258 SLC5A6 Seb Lunke Gene: slc5a6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1256 SLC5A7 Seb Lunke Gene: slc5a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1256 SLC5A7 Seb Lunke Classified gene: SLC5A7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1256 SLC5A7 Seb Lunke Gene: slc5a7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1255 SLC5A7 Seb Lunke gene: SLC5A7 was added
gene: SLC5A7 was added to gNBS. Sources: Literature
Mode of inheritance for gene: SLC5A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A7 were set to 20301347
Phenotypes for gene: SLC5A7 were set to Myasthenic syndrome, congenital, 20, presynaptic, MIM# 617143
Review for gene: SLC5A7 was set to GREEN
Added comment: Established gene-disease association.

Childhood onset, severe neuromuscular disorder
(recessive disease)

Treatment: Salbutamol, Acetylcholine-esterase inhibitors

Non-genetic confirmatory test: repetitive nerve stimulation test
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.1254 SLC9A3 Seb Lunke Gene: slc9a3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1254 SLC9A3 Seb Lunke Classified gene: SLC9A3 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1254 SLC9A3 Seb Lunke Gene: slc9a3 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1252 ADA2 Seb Lunke Classified gene: ADA2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1252 ADA2 Seb Lunke Gene: ada2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1251 ADA2 Seb Lunke Gene: ada2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1250 IL7R Zornitza Stark Gene: il7r has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1250 IL7R Zornitza Stark reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1250 IL2RG Zornitza Stark Gene: il2rg has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1250 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1249 IKBKG Zornitza Stark Classified gene: IKBKG as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1249 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1248 IGSF1 Zornitza Stark Gene: igsf1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1247 IGLL1 Zornitza Stark Gene: igll1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1247 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1246 IGHMBP2 Zornitza Stark Classified gene: IGHMBP2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1246 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1245 IGHM Zornitza Stark Gene: ighm has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1245 IDUA Zornitza Stark Gene: idua has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1245 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Mucopolysaccharidosis Ih, MIM#607014 to Mucopolysaccharidosis type 1, MONDO:0001586
Genomic newborn screening: BabyScreen+ v0.1244 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type 1, MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1244 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1244 IDS Zornitza Stark Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II to Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900
Genomic newborn screening: BabyScreen+ v0.1243 IDS Zornitza Stark reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1243 IL10RA Zornitza Stark Gene: il10ra has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1243 IL10RA Zornitza Stark Phenotypes for gene: IL10RA were changed from Inflammatory bowel disease, MIM#613148 to Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148
Genomic newborn screening: BabyScreen+ v0.1242 IL10RA Zornitza Stark reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1242 INVS Zornitza Stark Gene: invs has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1242 INVS Zornitza Stark Phenotypes for gene: INVS were changed from Nephronophthisis 2 to Nephronophthisis 2, infantile, (MIM#602088)
Genomic newborn screening: BabyScreen+ v0.1241 INVS Zornitza Stark Classified gene: INVS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1241 INVS Zornitza Stark Gene: invs has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1240 INVS Zornitza Stark reviewed gene: INVS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nephronophthisis 2, infantile, (MIM#602088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1240 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1239 IQCB1 Zornitza Stark Classified gene: IQCB1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1239 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1238 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1238 IRF6 Zornitza Stark Gene: irf6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1237 IRF6 Zornitza Stark Classified gene: IRF6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1237 IRF6 Zornitza Stark Gene: irf6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1236 ISPD Zornitza Stark Gene: ispd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1235 ISPD Zornitza Stark Classified gene: ISPD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1235 ISPD Zornitza Stark Gene: ispd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1234 ITGA3 Zornitza Stark Gene: itga3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1234 ITGA3 Zornitza Stark Classified gene: ITGA3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1234 ITGA3 Zornitza Stark Gene: itga3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1233 ITGA3 Zornitza Stark reviewed gene: ITGA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1233 ITGB2 Zornitza Stark Gene: itgb2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1233 ITGB2 Zornitza Stark reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukocyte adhesion deficiency, MIM# 116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1233 ITGB4 Zornitza Stark Gene: itgb4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1233 ITGB4 Zornitza Stark Phenotypes for gene: ITGB4 were changed from Epidermolysis bullosa, junctional, with pyloric atresia to Epidermolysis bullosa of hands and feet, MIM# 131800; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Epidermolysis bullosa, junctional, with pyloric atresia, MIM# 226730
Genomic newborn screening: BabyScreen+ v0.1231 ITGB4 Zornitza Stark Classified gene: ITGB4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1231 ITGB4 Zornitza Stark Gene: itgb4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1230 ITGB4 Zornitza Stark reviewed gene: ITGB4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa of hands and feet, MIM# 131800, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650, Epidermolysis bullosa, junctional, with pyloric atresia, MIM# 226730; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1230 IYD Zornitza Stark Gene: iyd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1230 IYD Zornitza Stark reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1230 HK1 Zornitza Stark Gene: hk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1228 HK1 Zornitza Stark Classified gene: HK1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1228 HK1 Zornitza Stark Gene: hk1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1227 JAK3 Zornitza Stark Gene: jak3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1227 JAK3 Zornitza Stark reviewed gene: JAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: SCID, autosomal recessive, T-negative/B-positive type MIM# 600802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1227 JAG1 Zornitza Stark Gene: jag1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1226 JAG1 Zornitza Stark Classified gene: JAG1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1226 JAG1 Zornitza Stark Gene: jag1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1225 KCNJ1 Zornitza Stark Gene: kcnj1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1224 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1223 KCNA1 Zornitza Stark Classified gene: KCNA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1223 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1222 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1222 KARS Zornitza Stark Phenotypes for gene: KARS were changed from deafness with progressive leukodystrophy to Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Deafness, autosomal recessive 89, MIM# 613916; Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196
Genomic newborn screening: BabyScreen+ v0.1221 KARS Zornitza Stark reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy with or without deafness (LEPID), MIM#619147, Deafness, autosomal recessive 89, MIM# 613916, Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1221 KANSL1 Zornitza Stark Gene: kansl1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1220 KANSL1 Zornitza Stark Classified gene: KANSL1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1220 KANSL1 Zornitza Stark Gene: kansl1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1219 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1219 KCNJ2 Zornitza Stark Phenotypes for gene: KCNJ2 were changed from Andersen cardiodysrhythmic periodic paralysis to Andersen syndrome MIM#170390; Atrial fibrillation, familial, 9 MIM#613980; Short QT syndrome 3 MIM#609622
Genomic newborn screening: BabyScreen+ v0.1218 KCNJ2 Zornitza Stark Classified gene: KCNJ2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1218 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1217 KCNQ4 Zornitza Stark Gene: kcnq4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1216 KCNQ4 Zornitza Stark Classified gene: KCNQ4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1216 KCNQ4 Zornitza Stark Gene: kcnq4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1215 KBTBD13 Zornitza Stark Gene: kbtbd13 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1213 KBTBD13 Zornitza Stark Classified gene: KBTBD13 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1213 KBTBD13 Zornitza Stark Gene: kbtbd13 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1212 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1212 KCNT1 Zornitza Stark Classified gene: KCNT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1212 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1211 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1211 KCTD7 Zornitza Stark Phenotypes for gene: KCTD7 were changed from Epilepsy, progressive myoclonic to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726)
Genomic newborn screening: BabyScreen+ v0.1210 KCTD7 Zornitza Stark Classified gene: KCTD7 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1210 KCTD7 Zornitza Stark Gene: kctd7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1209 KCTD7 Zornitza Stark reviewed gene: KCTD7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM#611726); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1209 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1209 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from Mucopolysaccharidosis IIIC to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930
Genomic newborn screening: BabyScreen+ v0.1208 HGSNAT Zornitza Stark Classified gene: HGSNAT as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1208 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1207 HGSNAT Zornitza Stark reviewed gene: HGSNAT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1207 HGF Zornitza Stark Gene: hgf has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1207 HGF Zornitza Stark Phenotypes for gene: HGF were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 39, MIM# 608265
Genomic newborn screening: BabyScreen+ v0.1206 HGF Zornitza Stark reviewed gene: HGF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 39, MIM# 608265; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1206 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1205 HEXB Zornitza Stark Classified gene: HEXB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1205 HEXB Zornitza Stark Gene: hexb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1204 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1204 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from Tay-Sachs disease to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800
Genomic newborn screening: BabyScreen+ v0.1203 HEXA Zornitza Stark Classified gene: HEXA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1203 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1202 HEXA Zornitza Stark reviewed gene: HEXA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: GM2-gangliosidosis, several forms 272800, Tay-Sachs disease 272800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1202 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1200 HDAC8 Zornitza Stark Classified gene: HDAC8 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1200 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1199 GJC2 Zornitza Stark Gene: gjc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1199 GJC2 Zornitza Stark Phenotypes for gene: GJC2 were changed from Pelizaeus-Merzbacher-like disease to Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804; Lymphatic malformation 3 MIM#613480
Genomic newborn screening: BabyScreen+ v0.1197 GJC2 Zornitza Stark Classified gene: GJC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1197 GJC2 Zornitza Stark Gene: gjc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1196 GJC2 Zornitza Stark reviewed gene: GJC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 44, autosomal recessive MIM#613206, Leukodystrophy, hypomyelinating, 2 MIM#608804, Lymphatic malformation 3 MIM#613480; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1196 GJB1 Zornitza Stark Gene: gjb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1194 GJB1 Zornitza Stark Classified gene: GJB1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1194 GJB1 Zornitza Stark Gene: gjb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1193 GIF Zornitza Stark Gene: gif has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1193 GIF Zornitza Stark Phenotypes for gene: GIF were changed from Intrinsic factor deficiency, MIM# 261000; Intrinsic factor deficiency # 261000 to Intrinsic factor deficiency, MIM# 261000
Genomic newborn screening: BabyScreen+ v0.1191 GIF Zornitza Stark reviewed gene: GIF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intrinsic factor deficiency MIM#261000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1190 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1190 SLC13A5 Zornitza Stark reviewed gene: SLC13A5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1190 TNFRSF11A Zornitza Stark Gene: tnfrsf11a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1189 TNFRSF11B Zornitza Stark Gene: tnfrsf11b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1187 TNFRSF11B Zornitza Stark Classified gene: TNFRSF11B as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1187 TNFRSF11B Zornitza Stark Gene: tnfrsf11b has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1186 TNFSF11 Zornitza Stark Gene: tnfsf11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1186 TNFSF11 Zornitza Stark Phenotypes for gene: TNFSF11 were changed from Osteopetrosis, autosomal recessive 2 to Osteopetrosis, autosomal recessive 2 MIM#259710
Genomic newborn screening: BabyScreen+ v0.1184 TNFSF11 Zornitza Stark Classified gene: TNFSF11 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1184 TNFSF11 Zornitza Stark Gene: tnfsf11 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1183 TNFSF11 Zornitza Stark reviewed gene: TNFSF11: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 2 MIM#259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1183 TNNI2 Zornitza Stark Gene: tnni2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1183 TNNI2 Zornitza Stark Phenotypes for gene: TNNI2 were changed from Distal arthrogryposis syndrome 2b to Arthrogryposis, distal, type 2B1 MIM#601680
Genomic newborn screening: BabyScreen+ v0.1181 TNNI2 Zornitza Stark Classified gene: TNNI2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1181 TNNI2 Zornitza Stark Gene: tnni2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1180 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1178 TNNT1 Zornitza Stark Classified gene: TNNT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1178 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1177 TNNT3 Zornitza Stark Gene: tnnt3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1177 TNNT3 Zornitza Stark Phenotypes for gene: TNNT3 were changed from Arthyrgryposis, distal to Arthrogryposis, distal MIM#618435
Genomic newborn screening: BabyScreen+ v0.1175 TNNT3 Zornitza Stark Classified gene: TNNT3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1175 TNNT3 Zornitza Stark Gene: tnnt3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1174 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1172 TPM2 Zornitza Stark Gene: tpm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1172 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from Nemaline myopathy; Arthrogryposis multiplex congenita, distal to Arthrgryposis MIM#108120; Nemaline myopathy MIM#609285
Genomic newborn screening: BabyScreen+ v0.1170 TPM2 Zornitza Stark Classified gene: TPM2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1170 TPM2 Zornitza Stark Gene: tpm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1169 TPM3 Zornitza Stark Gene: tpm3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1169 TPM3 Zornitza Stark Phenotypes for gene: TPM3 were changed from Nemaline myopathy; Congenital fiber-type disproportion myopathy to CAP myopathy 1, MIM# 609284; Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284
Genomic newborn screening: BabyScreen+ v0.1167 TPM3 Zornitza Stark Classified gene: TPM3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1167 TPM3 Zornitza Stark Gene: tpm3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1166 SLC26A3 Seb Lunke Gene: slc26a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1165 SLC26A2 Seb Lunke Gene: slc26a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1165 SLC26A2 Seb Lunke Phenotypes for gene: SLC26A2 were changed from Achondrogenesis 1B to Achondrogenesis 1B, MIM#600972
Genomic newborn screening: BabyScreen+ v0.1164 SLC26A2 Seb Lunke Classified gene: SLC26A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1164 SLC26A2 Seb Lunke Gene: slc26a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1163 SLC26A2 Seb Lunke reviewed gene: SLC26A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Achondrogenesis 1B, MIM#600972; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1163 SLC25A4 Seb Lunke Gene: slc25a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1163 SLC25A4 Seb Lunke Phenotypes for gene: SLC25A4 were changed from Progressive external ophthalmoplegia to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418
Genomic newborn screening: BabyScreen+ v0.1161 SLC25A4 Seb Lunke Classified gene: SLC25A4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1161 SLC25A4 Seb Lunke Gene: slc25a4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1160 SLC16A1 Seb Lunke Gene: slc16a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1159 SLC16A1 Seb Lunke Classified gene: SLC16A1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1159 SLC16A1 Seb Lunke Gene: slc16a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1158 SLC13A5 Seb Lunke Classified gene: SLC13A5 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1158 SLC13A5 Seb Lunke Gene: slc13a5 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1157 SLC13A5 Seb Lunke gene: SLC13A5 was added
gene: SLC13A5 was added to gNBS. Sources: Literature
for review tags were added to gene: SLC13A5.
Mode of inheritance for gene: SLC13A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A5 were set to 29895383
Phenotypes for gene: SLC13A5 were set to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905
Review for gene: SLC13A5 was set to AMBER
Added comment: Established gene-disease association.

Childhood onset, neurological condition

Treatment: Ketogenic diet, stiripentol effective in one study of three related patients

Non-genetic confirmatory test: plasma and CSF citrate levels
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.1156 SLC25A38 Seb Lunke Gene: slc25a38 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1156 SLC25A38 Seb Lunke Phenotypes for gene: SLC25A38 were changed from Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive to Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950
Genomic newborn screening: BabyScreen+ v0.1155 SLC25A38 Seb Lunke reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1155 SLC25A20 Seb Lunke Gene: slc25a20 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1154 TNFRSF11A Lilian Downie changed review comment from: strong gene disease association
Infant onset osteopetrosis and immunodeficiency
No treatment



NB AD phenotype has later onset; to: strong gene disease association
Infant onset osteopetrosis and immunodeficiency
Treatment bone marrow transplant



NB AD phenotype has later onset
Genomic newborn screening: BabyScreen+ v0.1154 TNFSF11 Lilian Downie changed review comment from: Strong gene disease association (gene also known as RANKL)
Infant, early childhood onset increased bone density, lack of bone marrow cavity, stunted growth, macrocephaly, progressive deafness, blindness, hepatosplenomegaly, and severe anemia.
No treatment; to: Strong gene disease association (gene also known as RANKL)
Infant, early childhood onset increased bone density, lack of bone marrow cavity, stunted growth, macrocephaly, progressive deafness, blindness, hepatosplenomegaly, and severe anemia.
No treatment
Genomic newborn screening: BabyScreen+ v0.1154 TNFRSF11A Lilian Downie reviewed gene: TNFRSF11A: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 36031188, PMID: 35812760; Phenotypes: Osteopetrosis, autosomal recessive 7 - MIM# 612301; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1154 TNFSF11 Lilian Downie reviewed gene: TNFSF11: Rating: ; Mode of pathogenicity: None; Publications: PMID:17632511, PMID: 36031188, PMID: 32940787; Phenotypes: Osteopetrosis, autosomal recessive 2 MIM#259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1154 TNNI2 Lilian Downie reviewed gene: TNNI2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34502093; Phenotypes: Arthrogryposis, distal, type 2B1 MIM#601680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1154 TNNT3 Lilian Downie reviewed gene: TNNT3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 19309503; Phenotypes: Arthrogryposis, distal MIM#618435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1154 TPM2 Lilian Downie reviewed gene: TPM2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 27726070; Phenotypes: Arthrgryposis MIM#108120, Nemaline myopathy MIM#609285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1154 GRHPR John Christodoulou reviewed gene: GRHPR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301742; Phenotypes: nephrolithiasis, haematuria, renal colic, obstruction of the urinary tract, Nephrocalcinosis, End-stage renal disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1154 GNPTG John Christodoulou reviewed gene: GNPTG: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301784; Phenotypes: Growth rate deceleration, Joint stiffness of the fingers, shoulders, and hips, Gradual mild coarsening of facial features, Genu valgum, scoliosis, hyperlordosis, mitral valve thickening; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1154 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1154 SLC25A19 Zornitza Stark Classified gene: SLC25A19 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1154 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1153 SLC25A19 Zornitza Stark reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1152 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1152 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1151 SLC25A15 Seb Lunke Gene: slc25a15 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1150 SLC25A13 Seb Lunke Gene: slc25a13 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1149 SLC25A13 Seb Lunke Classified gene: SLC25A13 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1149 SLC25A13 Seb Lunke Gene: slc25a13 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1148 SLC25A19 Seb Lunke gene: SLC25A19 was added
gene: SLC25A19 was added to gNBS. Sources: Literature
for review tags were added to gene: SLC25A19.
Mode of inheritance for gene: SLC25A19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A19 were set to 31095747
Phenotypes for gene: SLC25A19 were set to Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710
Review for gene: SLC25A19 was set to AMBER
Added comment: Established gene-disease association.

Onset of acute encephalopathic attacks in childhood (3 to 7 years) often after febrile illness, full recovery after attacks. Onset of chronic progressive polyneuropathy in late childhood.

Treatment: 5 patients treated with thiamine supplementation, which led to a substantial improvement in peripheral neuropathy and gait in early treated patients

Non-genetic confirmatory test: No
Sources: Literature
Genomic newborn screening: BabyScreen+ v0.1147 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1147 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from Neutropenia, severe congenital 3, autosomal recessive, MIM# 610738 to Neutropenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Genomic newborn screening: BabyScreen+ v0.1146 HAX1 Zornitza Stark reviewed gene: HAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738, Kostmann syndrome MONDO:0012548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1146 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1146 HARS2 Zornitza Stark Phenotypes for gene: HARS2 were changed from Perrault syndrome; autosomal recessive sensorineural hearing loss to Perrault syndrome 2, MIM# 614926
Genomic newborn screening: BabyScreen+ v0.1145 HARS2 Zornitza Stark Classified gene: HARS2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1145 HARS2 Zornitza Stark Gene: hars2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1144 TRIM32 Zornitza Stark Gene: trim32 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1144 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from Muscular dystrophy, limb-girdle, type 2H to Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Genomic newborn screening: BabyScreen+ v0.1142 TRIM32 Zornitza Stark Classified gene: TRIM32 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1142 TRIM32 Zornitza Stark Gene: trim32 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1141 TREX1 Zornitza Stark Gene: trex1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1139 TREX1 Zornitza Stark Classified gene: TREX1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1139 TREX1 Zornitza Stark Gene: trex1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1138 TRAPPC2 Zornitza Stark Gene: trappc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1138 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from Spondyloepiphyseal dysplasia tarda to Spondyloepiphyseal dysplasia tarda MIM#313400
Genomic newborn screening: BabyScreen+ v0.1136 TRAPPC2 Zornitza Stark Classified gene: TRAPPC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1136 TRAPPC2 Zornitza Stark Gene: trappc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1135 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1135 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from Neuronal ceroid lipofuscinosis to Ceroid lipofuscinosis, neuronal, 2 MIM#204500 (Batten disease)
Genomic newborn screening: BabyScreen+ v0.1133 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1133 TPO Zornitza Stark Phenotypes for gene: TPO were changed from Thyroid dyshormonogenesis 2A to Thyroid dyshormonogenesis 2A MIM#274500
Genomic newborn screening: BabyScreen+ v0.1132 HADH Zornitza Stark Gene: hadh has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1131 GOT2 Zornitza Stark Gene: got2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1131 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1131 GPC3 Zornitza Stark Phenotypes for gene: GPC3 were changed from Simpson-Golabi-Behmel syndrome to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Genomic newborn screening: BabyScreen+ v0.1130 GPC3 Zornitza Stark Classified gene: GPC3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1130 GPC3 Zornitza Stark Gene: gpc3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1129 GPC3 Zornitza Stark reviewed gene: GPC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1129 GPR143 Zornitza Stark Gene: gpr143 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1128 GPR143 Zornitza Stark Classified gene: GPR143 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1128 GPR143 Zornitza Stark Gene: gpr143 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1127 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1126 GPSM2 Zornitza Stark Classified gene: GPSM2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1126 GPSM2 Zornitza Stark Gene: gpsm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1125 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1125 GRHL2 Zornitza Stark Phenotypes for gene: GRHL2 were changed from Autosomal dominant hearing loss, MIM# 608641 to Ectodermal dysplasia/short stature syndrome MIM#616029; Corneal dystrophy, posterior polymorphous, 4, MIM# 618031; Deafness, autosomal dominant 28, MIM# 608641
Genomic newborn screening: BabyScreen+ v0.1123 GRHL2 Zornitza Stark Classified gene: GRHL2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1123 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1122 GRHL2 Zornitza Stark reviewed gene: GRHL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia/short stature syndrome MIM#616029, Corneal dystrophy, posterior polymorphous, 4, MIM# 618031, Deafness, autosomal dominant 28, MIM# 608641; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1121 TPO Lilian Downie reviewed gene: TPO: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 15863666; Phenotypes: Thyroid dyshormonogenesis 2A MIM#274500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1121 TPP1 Lilian Downie reviewed gene: TPP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32684372, PMID: 31884868, PMID: 30470609, PMID: 33882967; Phenotypes: Ceroid lipofuscinosis, neuronal, 2 MIM#204500 (Batten disease); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1121 TRAPPC2 Lilian Downie reviewed gene: TRAPPC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301324; Phenotypes: Spondyloepiphyseal dysplasia tarda MIM#313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.1121 TRIM32 Lilian Downie reviewed gene: TRIM32: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21496629, PMID: 23142638; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1121 GRHPR Zornitza Stark Gene: grhpr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1121 GRXCR1 Zornitza Stark Gene: grxcr1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1121 GRXCR1 Zornitza Stark reviewed gene: GRXCR1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 25, MIM# 613285; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1121 GSS Zornitza Stark Gene: gss has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1120 GSS Zornitza Stark Classified gene: GSS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1120 GSS Zornitza Stark Gene: gss has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1119 GUSB Zornitza Stark Gene: gusb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1119 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1119 GCM2 Zornitza Stark Classified gene: GCM2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.1119 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1117 GUSB Zornitza Stark reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis VII, MIM# 253220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1117 GYS2 Zornitza Stark Gene: gys2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1116 GNPTAB Zornitza Stark Gene: gnptab has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1116 GNPTAB Zornitza Stark Phenotypes for gene: GNPTAB were changed from Mucolipidosis II to Mucolipidosis II alpha/beta, MIM# 252500, MONDO:0009650; Mucolipidosis III alpha/beta, MIM# 252600, MONDO:0018931
Genomic newborn screening: BabyScreen+ v0.1115 GNPTAB Zornitza Stark Classified gene: GNPTAB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1115 GNPTAB Zornitza Stark Gene: gnptab has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1114 GNPTAB Zornitza Stark reviewed gene: GNPTAB: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucolipidosis II alpha/beta, MIM# 252500, MONDO:0009650, Mucolipidosis III alpha/beta, MIM# 252600, MONDO:0018931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1114 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1114 GNE Zornitza Stark Phenotypes for gene: GNE were changed from Inclusion body myopathy to Nonaka myopathy, MIM# 605820
Genomic newborn screening: BabyScreen+ v0.1113 GNE Zornitza Stark Classified gene: GNE as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1113 GNE Zornitza Stark Gene: gne has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1112 GNE Zornitza Stark Classified gene: GNE as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1112 GNE Zornitza Stark Gene: gne has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1111 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1111 GJA1 Zornitza Stark Phenotypes for gene: GJA1 were changed from Oculodentodigital dysplasia to Oculodentodigital dysplasia, autosomal recessive, MIM# 257850; Oculodentodigital dysplasia, MIM# 164200
Genomic newborn screening: BabyScreen+ v0.1109 GJA1 Zornitza Stark Classified gene: GJA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1109 GJA1 Zornitza Stark Gene: gja1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1108 GJA1 Zornitza Stark reviewed gene: GJA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculodentodigital dysplasia, autosomal recessive, MIM# 257850, Oculodentodigital dysplasia, MIM# 164200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1108 GIPC3 Zornitza Stark Gene: gipc3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1108 GIPC3 Zornitza Stark Phenotypes for gene: GIPC3 were changed from Hearing loss to Deafness, autosomal recessive 15, MIM# 601869
Genomic newborn screening: BabyScreen+ v0.1107 GIPC3 Zornitza Stark reviewed gene: GIPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 15, MIM# 601869; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1107 GLI3 Zornitza Stark Gene: gli3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1106 GLI3 Zornitza Stark Classified gene: GLI3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1106 GLI3 Zornitza Stark Gene: gli3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1105 CRLF1 Zornitza Stark Gene: crlf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1104 CRLF1 Zornitza Stark Classified gene: CRLF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1104 CRLF1 Zornitza Stark Gene: crlf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1103 SLC19A2 Zornitza Stark Gene: slc19a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1103 SLC25A1 Seb Lunke Gene: slc25a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1102 SLC25A1 Seb Lunke Classified gene: SLC25A1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1102 SLC25A1 Seb Lunke Gene: slc25a1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1099 SLC19A3 Seb Lunke Gene: slc19a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1099 SLC19A3 Seb Lunke Phenotypes for gene: SLC19A3 were changed from Basal ganglia disease, biotin-responsive, MIM#607483 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Genomic newborn screening: BabyScreen+ v0.1097 SLC19A3 Seb Lunke reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24260777; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1097 SLC19A2 Seb Lunke Gene: slc19a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1097 SLC19A2 Seb Lunke Phenotypes for gene: SLC19A2 were changed from Thiamine-responsive megaloblastic anemia syndrome to Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270
Genomic newborn screening: BabyScreen+ v0.1095 SLC19A2 Seb Lunke reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301459; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1095 SLC18A3 Seb Lunke Gene: slc18a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1094 SLC18A2 Seb Lunke changed review comment from: Established gene-disease association.

Childhood onset neurological condition.

Treatment: L-dopa resulted in severe exacerbation of the symptoms. Dopamine receptor agonist (pramipexole) resulted in improvement in symptoms. Earlier treatment more beneficial. Evidence from single family with benefits shown in 4 affected children.

Non-genetic confirmatory test: blood pressure measurement and sodium, potassium, aldosterone, renin levels; to: Established gene-disease association.

Childhood onset neurological condition.

Treatment: L-dopa resulted in severe exacerbation of the symptoms. Dopamine receptor agonist (pramipexole) resulted in improvement in symptoms. Earlier treatment more beneficial. Evidence from single family with benefits shown in 4 affected children.

Non-genetic confirmatory test: whole blood serotonin level
Genomic newborn screening: BabyScreen+ v0.1094 SLC18A2 Seb Lunke Gene: slc18a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1094 KDM6A Zornitza Stark Gene: kdm6a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1092 KDM6A Zornitza Stark Classified gene: KDM6A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1092 KDM6A Zornitza Stark Gene: kdm6a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1091 KIF21A Zornitza Stark Gene: kif21a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1091 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700of extraocular muscles, congenital to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Genomic newborn screening: BabyScreen+ v0.1090 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital to Fibrosis Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700of extraocular muscles, congenital
Genomic newborn screening: BabyScreen+ v0.1089 KIF21A Zornitza Stark Classified gene: KIF21A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1089 KIF21A Zornitza Stark Gene: kif21a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1088 KIF21A Zornitza Stark reviewed gene: KIF21A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1088 KIT Zornitza Stark Gene: kit has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1087 KIT Zornitza Stark Classified gene: KIT as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1087 KIT Zornitza Stark Gene: kit has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1086 KLF1 Zornitza Stark Gene: klf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1085 KLF1 Zornitza Stark Classified gene: KLF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1085 KLF1 Zornitza Stark Gene: klf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1084 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1084 KLHL40 Zornitza Stark Phenotypes for gene: KLHL40 were changed from Nemaline myopathy to Nemaline myopathy 8, autosomal recessive, MIM# 615348
Genomic newborn screening: BabyScreen+ v0.1083 KLHL40 Zornitza Stark Classified gene: KLHL40 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1083 KLHL40 Zornitza Stark Gene: klhl40 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1082 KLHL40 Zornitza Stark reviewed gene: KLHL40: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 8, autosomal recessive, MIM# 615348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1082 KLHL41 Zornitza Stark Gene: klhl41 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1081 KLHL41 Zornitza Stark Classified gene: KLHL41 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1081 KLHL41 Zornitza Stark Gene: klhl41 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1080 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1078 KAT6B Zornitza Stark Classified gene: KAT6B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1078 KAT6B Zornitza Stark Gene: kat6b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1077 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1076 KMT2D Zornitza Stark Classified gene: KMT2D as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1076 KMT2D Zornitza Stark Gene: kmt2d has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1075 KRT14 Zornitza Stark Gene: krt14 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1075 KRT14 Zornitza Stark Phenotypes for gene: KRT14 were changed from Epidermolysis bullosa simplex to Epidermolysis bullosa simplex, recessive 1, 601001; Dermatopathia pigmentosa reticularis, 125595; Epidermolysis bullosa simplex, Dowling-Meara type, 131760; Epidermolysis bullosa simplex, Koebner type, 131900; Epidermolysis bullosa simplex, Weber-Cockayne type, 131800; Naegeli-Franceschetti-Jadassohn syndrome, 161000
Genomic newborn screening: BabyScreen+ v0.1073 KRT14 Zornitza Stark Classified gene: KRT14 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1073 KRT14 Zornitza Stark Gene: krt14 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1072 KRT14 Zornitza Stark reviewed gene: KRT14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa simplex, recessive 1, 601001, Dermatopathia pigmentosa reticularis, 125595, Epidermolysis bullosa simplex, Dowling-Meara type, 131760, Epidermolysis bullosa simplex, Koebner type, 131900, Epidermolysis bullosa simplex, Weber-Cockayne type, 131800, Naegeli-Franceschetti-Jadassohn syndrome, 161000; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1072 KRT16 Zornitza Stark Gene: krt16 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1071 KRT16 Zornitza Stark Classified gene: KRT16 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1071 KRT16 Zornitza Stark Gene: krt16 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1070 KRT17 Zornitza Stark Gene: krt17 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1069 KRT17 Zornitza Stark Classified gene: KRT17 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1069 KRT17 Zornitza Stark Gene: krt17 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1068 KRT5 Zornitza Stark Gene: krt5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1068 KRT5 Zornitza Stark Phenotypes for gene: KRT5 were changed from Epidermolysis bullosa simplex to Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MCR, MIM# 609352; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800
Genomic newborn screening: BabyScreen+ v0.1066 KRT5 Zornitza Stark Classified gene: KRT5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1066 KRT5 Zornitza Stark Gene: krt5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1065 KRT5 Zornitza Stark reviewed gene: KRT5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dowling-Degos disease 1, MIM# 179850, Epidermolysis bullosa simplex-MCR, MIM# 609352, Epidermolysis bullosa simplex-MP 131960, Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760, Epidermolysis bullosa simplex, Koebner type, MIM# 131900, Epidermolysis bullosa simplex, recessive 1, MIM# 601001, Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1065 KRT6A Zornitza Stark Gene: krt6a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1064 KRT6A Zornitza Stark Classified gene: KRT6A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1064 KRT6A Zornitza Stark Gene: krt6a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1063 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1062 PTPN11 Zornitza Stark Classified gene: PTPN11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1062 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1061 KRAS Zornitza Stark Gene: kras has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1060 KRAS Zornitza Stark Classified gene: KRAS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1060 KRAS Zornitza Stark Gene: kras has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1059 HRAS Zornitza Stark Gene: hras has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1058 HRAS Zornitza Stark Classified gene: HRAS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1058 HRAS Zornitza Stark Gene: hras has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1057 HINT1 Zornitza Stark Gene: hint1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1057 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from Axonal neuropathy with neuromyotonia to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
Genomic newborn screening: BabyScreen+ v0.1056 HINT1 Zornitza Stark Classified gene: HINT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1056 HINT1 Zornitza Stark Gene: hint1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1055 HINT1 Zornitza Stark reviewed gene: HINT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1055 FAM126A Zornitza Stark Gene: fam126a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1054 FAM126A Zornitza Stark Classified gene: FAM126A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1054 FAM126A Zornitza Stark Gene: fam126a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1052 BMPR1A Zornitza Stark changed review comment from: Well established gene-disease association.

Polyposis: onset in childhood although cancer onset tends to be in adulthood.

For review.; to: Well established gene-disease association.

Polyposis: onset in childhood although cancer onset tends to be in adulthood.

Screening typically starts in adolescence.
Genomic newborn screening: BabyScreen+ v0.1052 CASQ2 Zornitza Stark Classified gene: CASQ2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1052 CASQ2 Zornitza Stark Gene: casq2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1051 ERCC5 Zornitza Stark changed review comment from: Bi-allelic variants cause a range of DNA repair disorders.

Variable severity and age of onset of manifestations.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.

For discussion.; to: Bi-allelic variants cause a range of DNA repair disorders.

Variable severity and age of onset of manifestations.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.
Genomic newborn screening: BabyScreen+ v0.1051 TSC1 Zornitza Stark Classified gene: TSC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1051 TSC1 Zornitza Stark Gene: tsc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1050 TSC1 Zornitza Stark reviewed gene: TSC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis-1 MIM#191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1050 TSC2 Zornitza Stark Classified gene: TSC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1050 TSC2 Zornitza Stark Gene: tsc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1049 TSC2 Zornitza Stark reviewed gene: TSC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tuberous sclerosis-2 MIM#613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1049 TTC7A Zornitza Stark Classified gene: TTC7A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1049 TTC7A Zornitza Stark Gene: ttc7a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1048 ERCC2 Zornitza Stark Classified gene: ERCC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1048 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1047 ERCC2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE.

DNA repair disorder.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.

For discussion.; to: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE.

DNA repair disorder.

Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil.
Genomic newborn screening: BabyScreen+ v0.1045 FBN1 Zornitza Stark Classified gene: FBN1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.1045 FBN1 Zornitza Stark Gene: fbn1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.1044 FAM161A Zornitza Stark Gene: fam161a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1043 FAM161A Zornitza Stark Classified gene: FAM161A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1043 FAM161A Zornitza Stark Gene: fam161a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1042 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1042 FAM20C Zornitza Stark Phenotypes for gene: FAM20C were changed from Osteosclerotic bone dysplasia to Raine syndrome, MIM# 259775
Genomic newborn screening: BabyScreen+ v0.1041 FAM20C Zornitza Stark Classified gene: FAM20C as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1041 FAM20C Zornitza Stark Gene: fam20c has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1040 FAM58A Zornitza Stark Gene: fam58a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1039 FAM58A Zornitza Stark Classified gene: FAM58A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1039 FAM58A Zornitza Stark Gene: fam58a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1038 FANCA Zornitza Stark Gene: fanca has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1037 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1036 FANCC Zornitza Stark Gene: fancc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1035 FANCD2 Zornitza Stark Gene: fancd2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1034 FANCG Zornitza Stark Gene: fancg has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1034 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1034 FAS Zornitza Stark Gene: fas has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1034 FAS Zornitza Stark Classified gene: FAS as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1034 FAS Zornitza Stark Gene: fas has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1033 FBN1 Zornitza Stark Gene: fbn1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1032 FBN1 Zornitza Stark Classified gene: FBN1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1032 FBN1 Zornitza Stark Gene: fbn1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1031 GDAP1 Zornitza Stark Gene: gdap1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1031 GDAP1 Zornitza Stark Phenotypes for gene: GDAP1 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2K, MIM#607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM#607706; Charcot-Marie-Tooth disease, recessive intermediate, A, MIM#608340; Charcot-Marie-Tooth disease, type 4A, MIM#214400
Genomic newborn screening: BabyScreen+ v0.1028 GDAP1 Zornitza Stark Classified gene: GDAP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1028 GDAP1 Zornitza Stark Gene: gdap1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1027 FERMT3 Zornitza Stark Gene: fermt3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1027 FERMT3 Zornitza Stark reviewed gene: FERMT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukocyte adhesion deficiency, type III, MIM# 612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1027 FGA Zornitza Stark Gene: fga has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1026 FGB Zornitza Stark Gene: fgb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1025 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1024 FGD1 Zornitza Stark Classified gene: FGD1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1024 FGD1 Zornitza Stark Gene: fgd1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1023 FGD4 Zornitza Stark Gene: fgd4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1022 FGD4 Zornitza Stark Classified gene: FGD4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1022 FGD4 Zornitza Stark Gene: fgd4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1021 FGF3 Zornitza Stark Gene: fgf3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1021 FGF3 Zornitza Stark Phenotypes for gene: FGF3 were changed from Deafness, congenital with inner ear agenesis, microtia, and microdontia to Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706
Genomic newborn screening: BabyScreen+ v0.1020 FGF3 Zornitza Stark reviewed gene: FGF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, congenital with inner ear agenesis, microtia, and microdontia, MIM# 610706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.1020 FBN2 Zornitza Stark Gene: fbn2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1020 FBN2 Zornitza Stark Classified gene: FBN2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1020 FBN2 Zornitza Stark Gene: fbn2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1019 SLC34A3 Zornitza Stark Gene: slc34a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1018 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1018 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from Kallmann syndrome to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Pfeiffer syndrome 101600; Trigonocephaly 1 190440
Genomic newborn screening: BabyScreen+ v0.1017 FGFR1 Zornitza Stark Classified gene: FGFR1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1017 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1016 FGFR1 Zornitza Stark reviewed gene: FGFR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1016 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1016 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from Jackson-Weiss syndrome; Apert syndrome; Crouzon syndrome; Pfeiffer syndrome; Beare-Stevenson cutis gyrata syndrome to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410; Apert syndrome, MIM# 101200; Beare-Stevenson cutis gyrata syndrome, MIM# 123790; Bent bone dysplasia syndrome, MIM# 614592; Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600; Crouzon syndrome , MIM#123500; Jackson-Weiss syndrome,MIM# 123150; LADD syndrome, MIM# 149730; Pfeiffer syndrome,MIM# 101600; Saethre-Chotzen syndrome 101400
Genomic newborn screening: BabyScreen+ v0.1015 FGFR2 Zornitza Stark Classified gene: FGFR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1015 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1014 FGFR2 Zornitza Stark reviewed gene: FGFR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592, Craniofacial-skeletal-dermatologic dysplasia, MIM# 101600, Crouzon syndrome , MIM#123500, Jackson-Weiss syndrome,MIM# 123150, LADD syndrome, MIM# 149730, Pfeiffer syndrome,MIM# 101600, Saethre-Chotzen syndrome 101400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1014 FGFR3 Zornitza Stark Gene: fgfr3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1014 FGFR3 Zornitza Stark Phenotypes for gene: FGFR3 were changed from Muenke syndrome; Thanatophoric dysplasia type 1; Crouzon syndrome with acanthosis nigricans; LADD syndrome; Hypochondroplasia; Achondroplasia; CATSHL syndrome to Achondroplasia MONDO:0007037
Genomic newborn screening: BabyScreen+ v0.1012 FGFR3 Zornitza Stark reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34341520, 31269546; Phenotypes: Achondroplasia MONDO:0007037; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.1012 FGG Zornitza Stark Gene: fgg has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1011 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1010 FKRP Zornitza Stark Classified gene: FKRP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1010 FKRP Zornitza Stark Gene: fkrp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1009 FKTN Zornitza Stark Gene: fktn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1008 FKTN Zornitza Stark Classified gene: FKTN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1008 FKTN Zornitza Stark Gene: fktn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1007 FLCN Zornitza Stark Gene: flcn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1006 FLCN Zornitza Stark Classified gene: FLCN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1006 FLCN Zornitza Stark Gene: flcn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1005 FLNA Zornitza Stark Gene: flna has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1005 FLNA Zornitza Stark Phenotypes for gene: FLNA were changed from Otopalatodigital spectrum disorder to FLNA-related disorders; Frontometaphyseal dysplasia 305620; Otopalatodigital syndrome, type II -304120; Osteodysplasty Melnick Needles 309350; Melnick Needles syndrome 309350; Otopalatodigital syndrome, type II 304120; Frontometaphyseal dysplasia 305620; Terminal osseous dysplasia 300244; Otopalatodigital syndrome, type I -311300
Genomic newborn screening: BabyScreen+ v0.1004 FLNA Zornitza Stark Classified gene: FLNA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1004 FLNA Zornitza Stark Gene: flna has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1003 FLNA Zornitza Stark reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: FLNA-related disorders, Frontometaphyseal dysplasia 305620, Otopalatodigital syndrome, type II -304120, Osteodysplasty Melnick Needles 309350, Melnick Needles syndrome 309350, Otopalatodigital syndrome, type II 304120, Frontometaphyseal dysplasia 305620, Terminal osseous dysplasia 300244, Otopalatodigital syndrome, type I -311300; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.1003 FOXA2 Zornitza Stark Gene: foxa2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.1001 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.1000 FOXC1 Zornitza Stark Classified gene: FOXC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.1000 FOXC1 Zornitza Stark Gene: foxc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.999 FOXC2 Zornitza Stark Gene: foxc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.999 FOXC2 Zornitza Stark Phenotypes for gene: FOXC2 were changed from Lymphoedema, primary to Lymphoedema-distichiasis syndrome, MIM# 153400
Genomic newborn screening: BabyScreen+ v0.998 FOXC2 Zornitza Stark Classified gene: FOXC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.998 FOXC2 Zornitza Stark Gene: foxc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.997 FOXC2 Zornitza Stark reviewed gene: FOXC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lymphoedema-distichiasis syndrome, MIM# 153400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.997 FOXF1 Zornitza Stark Gene: foxf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.997 FOXF1 Zornitza Stark Phenotypes for gene: FOXF1 were changed from Alveolar capillary dysplasia with misalignment of pulmonary veins to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
Genomic newborn screening: BabyScreen+ v0.996 FOXF1 Zornitza Stark Classified gene: FOXF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.996 FOXF1 Zornitza Stark Gene: foxf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.995 FOXF1 Zornitza Stark reviewed gene: FOXF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.995 FOXI1 Zornitza Stark Gene: foxi1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.995 FOXI1 Zornitza Stark Phenotypes for gene: FOXI1 were changed from sensorineural deafness and distal renal tubular acidosis to autosomal recessive distal renal tubular acidosis MONDO:0018440
Genomic newborn screening: BabyScreen+ v0.994 FOXI1 Zornitza Stark Classified gene: FOXI1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.994 FOXI1 Zornitza Stark Gene: foxi1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.993 FOXI1 Zornitza Stark reviewed gene: FOXI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive distal renal tubular acidosis MONDO:0018440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.993 FOXP3 Zornitza Stark Gene: foxp3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.992 FRAS1 Zornitza Stark Gene: fras1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.991 FRAS1 Zornitza Stark Classified gene: FRAS1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.991 FRAS1 Zornitza Stark Gene: fras1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.990 GLDC Zornitza Stark Gene: gldc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.988 GLDC Zornitza Stark Classified gene: GLDC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.988 GLDC Zornitza Stark Gene: gldc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.987 GLB1 Zornitza Stark Gene: glb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.987 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from Gangliosidosis GM1 to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Genomic newborn screening: BabyScreen+ v0.985 GLB1 Zornitza Stark Classified gene: GLB1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.985 GLB1 Zornitza Stark Gene: glb1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.984 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type I MIM#230500, GM1-gangliosidosis, type II MIM# 230600, GM1-gangliosidosis, type III MIM#230650, Mucopolysaccharidosis type IVB (Morquio) MIM#253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.984 F10 Zornitza Stark Gene: f10 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.984 F10 Zornitza Stark Classified gene: F10 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.984 F10 Zornitza Stark Gene: f10 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.983 FTL Zornitza Stark Gene: ftl has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.982 FTL Zornitza Stark Classified gene: FTL as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.982 FTL Zornitza Stark Gene: ftl has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.981 FXN Zornitza Stark Gene: fxn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.980 FXN Zornitza Stark Classified gene: FXN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.980 FXN Zornitza Stark Gene: fxn has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.979 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.978 EZH2 Zornitza Stark Classified gene: EZH2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.978 EZH2 Zornitza Stark Gene: ezh2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.977 EYA4 Zornitza Stark Gene: eya4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.976 EYA4 Zornitza Stark Classified gene: EYA4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.976 EYA4 Zornitza Stark Gene: eya4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.975 EYA1 Zornitza Stark Gene: eya1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.974 EYA1 Zornitza Stark Classified gene: EYA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.974 EYA1 Zornitza Stark Gene: eya1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.973 EXT2 Zornitza Stark Gene: ext2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.973 EXT2 Zornitza Stark Phenotypes for gene: EXT2 were changed from Exostoses, multiple, type 2 to Seizures, scoliosis, and macrocephaly syndrome, MIM#616682
Genomic newborn screening: BabyScreen+ v0.971 EXT2 Zornitza Stark Classified gene: EXT2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.971 EXT2 Zornitza Stark Gene: ext2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.970 EXT2 Zornitza Stark reviewed gene: EXT2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Seizures, scoliosis, and macrocephaly syndrome, MIM#616682; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.970 EXT1 Zornitza Stark Gene: ext1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.969 EXT1 Zornitza Stark Classified gene: EXT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.969 EXT1 Zornitza Stark Gene: ext1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.968 EVC2 Zornitza Stark Gene: evc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.968 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from Ellis-van Creveld syndrome to Ellis-van Creveld syndrome, MIM# 225500; Weyers acrofacial dysostosis, MIM# 193530
Genomic newborn screening: BabyScreen+ v0.966 EVC2 Zornitza Stark Classified gene: EVC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.966 EVC2 Zornitza Stark Gene: evc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.965 EVC2 Zornitza Stark reviewed gene: EVC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ellis-van Creveld syndrome, MIM# 225500, Weyers acrofacial dysostosis, MIM# 193530; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.965 EVC Zornitza Stark Gene: evc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.964 EVC Zornitza Stark Classified gene: EVC as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.964 EVC Zornitza Stark Gene: evc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.963 EFTUD2 Zornitza Stark Classified gene: EFTUD2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.963 EFTUD2 Zornitza Stark Gene: eftud2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.962 ESRRB Zornitza Stark Gene: esrrb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.962 ESRRB Zornitza Stark Phenotypes for gene: ESRRB were changed from Hearing loss to Deafness, autosomal recessive 35, MIM#608565
Genomic newborn screening: BabyScreen+ v0.961 ESRRB Zornitza Stark reviewed gene: ESRRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 35, MIM#608565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.961 ESPN Zornitza Stark Gene: espn has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.961 ESPN Zornitza Stark reviewed gene: ESPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 36, MIM# 609006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.961 ESCO2 Zornitza Stark Gene: esco2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.960 ESCO2 Zornitza Stark Classified gene: ESCO2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.960 ESCO2 Zornitza Stark Gene: esco2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.959 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.958 ERCC8 Zornitza Stark Classified gene: ERCC8 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.958 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.957 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.957 ERCC6 Zornitza Stark Phenotypes for gene: ERCC6 were changed from Cockayne syndrome to Cerebrooculofacioskeletal syndrome 1, MIM# 214150 MONDO:0008955; Cockayne syndrome, type B, MIM# 133540 MONDO:0019570; De Sanctis-Cacchione syndrome, MIM# 278800 MONDO:0010217; UV-sensitive syndrome 1, MIM# 600630 MONDO:0010909
Genomic newborn screening: BabyScreen+ v0.956 ERCC6 Zornitza Stark Classified gene: ERCC6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.956 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.955 ERCC6 Zornitza Stark reviewed gene: ERCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrooculofacioskeletal syndrome 1, MIM# 214150 MONDO:0008955, Cockayne syndrome, type B, MIM# 133540 MONDO:0019570, De Sanctis-Cacchione syndrome, MIM# 278800 MONDO:0010217, UV-sensitive syndrome 1, MIM# 600630 MONDO:0010909; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.955 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.954 ERCC5 Zornitza Stark Classified gene: ERCC5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.954 ERCC5 Zornitza Stark Gene: ercc5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.953 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.952 ERCC2 Zornitza Stark Classified gene: ERCC2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.952 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.951 EPS8L2 Zornitza Stark Gene: eps8l2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.951 EPS8L2 Zornitza Stark Classified gene: EPS8L2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.951 EPS8L2 Zornitza Stark Gene: eps8l2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.950 EPS8L2 Zornitza Stark reviewed gene: EPS8L2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness autosomal recessive 106, MIM# 617637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.950 GLDC John Christodoulou changed review comment from: causes nonketotic hyperglycaemia

classical form presents in the neonatal period and treatments (eg sodium benzoate and NDMA receptor antagonists) do not alter the neurological trajectory

milder forms of the disorder (later onset, but still in early childhood), may show response to therapy (PMID: 21411353); potentially aided by phenotype-genotype correlations (PMID: 32421718); to: causes nonketotic hyperglycaemia

classical form presents in the neonatal period and treatments (eg sodium benzoate and NDMA receptor antagonists) do not alter the neurological trajectory

milder forms of the disorder (later onset, but still in early childhood), may show response to therapy (PMID: 21411353); potentially aided by phenotype-genotype correlations (PMID: 32421718)
Genomic newborn screening: BabyScreen+ v0.950 GLB1 John Christodoulou reviewed gene: GLB1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34539759; Phenotypes: neurodegeneration, coarse facial features, gingival hyperplasia, cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.950 GLA John Christodoulou reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30017653; Phenotypes: neuropathic pain, cardiomyopathy, cataract, agniokeratomata, deafness, hypohidrosis, stroke, renal failure; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.950 EPS8 Zornitza Stark Gene: eps8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.950 EPS8 Zornitza Stark Phenotypes for gene: EPS8 were changed from deafness MIM#600205 to Autosomal recessive nonsyndromic hearing loss 102, MIM#600205, MONDO:0014428
Genomic newborn screening: BabyScreen+ v0.949 EPS8 Zornitza Stark reviewed gene: EPS8: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Autosomal recessive nonsyndromic hearing loss 102, MIM# MONDO:0014428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.949 EPM2A Zornitza Stark Gene: epm2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.949 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) to Lafora disease MONDO:0009697
Genomic newborn screening: BabyScreen+ v0.948 EPM2A Zornitza Stark Classified gene: EPM2A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.948 EPM2A Zornitza Stark Gene: epm2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.947 ENPP1 Zornitza Stark Gene: enpp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.947 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from Arterial calcification, generalized, of infancy, 1 to Arterial calcification, generalized, of infancy, 1, MIM# 208000; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
Genomic newborn screening: BabyScreen+ v0.946 ENPP1 Zornitza Stark changed review comment from: Bi-allelic variants:
GACI: well established gene-disease association, multiple families and mouse models.

Hypophosphataemic rickets: multiple families reported, some with features of GACI.

Reported variants are spread throughout the phosphodiesterase catalytic domain and nuclease-like domain. No genotype-phenotype correlation, variability even within the same family. These likely represent a spectrum of a single disorder, rather than two distinct disorders.

Should be able to distinguish clinically.

Treatment: etidronate, anti-hypertensive, calcitriol and oral phosphate supplements; to: Bi-allelic variants:
GACI: well established gene-disease association, multiple families and mouse models.

Hypophosphataemic rickets: multiple families reported, some with features of GACI.

Reported variants are spread throughout the phosphodiesterase catalytic domain and nuclease-like domain. No genotype-phenotype correlation, variability even within the same family. These likely represent a spectrum of a single disorder, rather than two distinct disorders.

Should be able to distinguish clinically.

Onset is congenital/early infancy.

Treatment: etidronate, anti-hypertensive, calcitriol and oral phosphate supplements
Genomic newborn screening: BabyScreen+ v0.946 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arterial calcification, generalized, of infancy, 1, MIM# 208000, Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.946 TTC7A Zornitza Stark Gene: ttc7a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.945 TTC7A Zornitza Stark Classified gene: TTC7A as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.945 TTC7A Zornitza Stark Gene: ttc7a has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.944 TTC37 Zornitza Stark Gene: ttc37 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.942 TTC37 Zornitza Stark Classified gene: TTC37 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.942 TTC37 Zornitza Stark Gene: ttc37 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.941 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.939 TTC21B Zornitza Stark Classified gene: TTC21B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.939 TTC21B Zornitza Stark Gene: ttc21b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.938 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.937 TSR2 Zornitza Stark Classified gene: TSR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.937 TSR2 Zornitza Stark Gene: tsr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.936 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.933 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.931 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.931 TSEN54 Zornitza Stark Phenotypes for gene: TSEN54 were changed from Pontocerebellar hypoplasia type 4 to Pontocerebellar hypoplasia type 2A MIM#277470
Genomic newborn screening: BabyScreen+ v0.929 TSEN54 Zornitza Stark Classified gene: TSEN54 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.929 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.928 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.927 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.926 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.926 TRPM4 Zornitza Stark Phenotypes for gene: TRPM4 were changed from Cardiac conduction disease to Progressive familial heart block, type IB 604559
Genomic newborn screening: BabyScreen+ v0.924 TRPM4 Zornitza Stark Classified gene: TRPM4 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.924 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.923 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.923 TRMU Zornitza Stark Phenotypes for gene: TRMU were changed from Liver failure, transient infantile to Liver failure, transient infantile MIM# 613070
Genomic newborn screening: BabyScreen+ v0.921 TRIOBP Zornitza Stark Gene: triobp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.921 TRIOBP Zornitza Stark Phenotypes for gene: TRIOBP were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 28, MIM#609823
Genomic newborn screening: BabyScreen+ v0.919 TRIM37 Zornitza Stark Gene: trim37 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.917 TRIM37 Zornitza Stark Classified gene: TRIM37 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.917 TRIM37 Zornitza Stark Gene: trim37 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.915 ENG Zornitza Stark Classified gene: ENG as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.915 ENG Zornitza Stark Gene: eng has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.914 ENG Zornitza Stark changed review comment from: Well established gene disease association.

Clingen: strong actionability in adults
Although HHT is a developmental disorder and infants are occasionally severely affected, in most people the features are age-dependent and the diagnosis is not suspected until adolescence or later. The average age of onset for epistaxis is 12 years, with 50-80% of patients affected before the age of 20 and 78-96% developing it eventually. Most patients report the appearance of telangiectasia of the mouth, face, or hands 5-30 years after the onset of nose bleeds, most commonly during the third decade. GI bleeding, when present, usually presents in the 5th or 6th decades of life. Patients rarely develop significant GI bleeding before 40 years of age. Women are affected with GI bleeding in a ratio of 2-3:1. AVMs of the brain are typically present at birth, whereas those in the lung and liver typically develop over time. Hemorrhage is often the presenting symptom of cerebral AVMs, while visceral AVMs may cause transient ischemic attacks, embolic stroke, and cerebral or other abscesses. Hepatic AVMs can present as high-output heart failure, portal hypertension, or biliary disease.

However, screening guidelines recommend screening for cerebral AVMs in first 6 months of life or at diagnosis (MRI).

For review.; to: Well established gene disease association.

Clingen: strong actionability in adults
Although HHT is a developmental disorder and infants are occasionally severely affected, in most people the features are age-dependent and the diagnosis is not suspected until adolescence or later. The average age of onset for epistaxis is 12 years, with 50-80% of patients affected before the age of 20 and 78-96% developing it eventually. Most patients report the appearance of telangiectasia of the mouth, face, or hands 5-30 years after the onset of nose bleeds, most commonly during the third decade. GI bleeding, when present, usually presents in the 5th or 6th decades of life. Patients rarely develop significant GI bleeding before 40 years of age. Women are affected with GI bleeding in a ratio of 2-3:1. AVMs of the brain are typically present at birth, whereas those in the lung and liver typically develop over time. Hemorrhage is often the presenting symptom of cerebral AVMs, while visceral AVMs may cause transient ischemic attacks, embolic stroke, and cerebral or other abscesses. Hepatic AVMs can present as high-output heart failure, portal hypertension, or biliary disease.

However, screening guidelines recommend screening for cerebral AVMs in first 6 months of life or at diagnosis (MRI). Management guidelines also suggest screening in asymptomatic children for pulmonary AVMs, PMID 32894695.
Genomic newborn screening: BabyScreen+ v0.914 ENG Zornitza Stark Gene: eng has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.914 ENG Zornitza Stark Phenotypes for gene: ENG were changed from Telangiectasia, hereditary hemorrhagic, type 1 to Telangiectasia, hereditary hemorrhagic, type 1 MIM#187300
Genomic newborn screening: BabyScreen+ v0.913 ENG Zornitza Stark Classified gene: ENG as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.913 ENG Zornitza Stark Gene: eng has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.912 ENG Zornitza Stark reviewed gene: ENG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 1 MIM#187300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.912 EMD Zornitza Stark Gene: emd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.911 EMD Zornitza Stark Classified gene: EMD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.911 EMD Zornitza Stark Gene: emd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.910 ELP1 Zornitza Stark Gene: elp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.908 ELP1 Zornitza Stark Classified gene: ELP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.908 ELP1 Zornitza Stark Gene: elp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.907 ELN Zornitza Stark Gene: eln has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.907 ELN Zornitza Stark Phenotypes for gene: ELN were changed from Supravalvar aortic stenosis to cutis laxa, autosomal dominant 1 MONDO:0007411; supravalvular aortic stenosis MONDO:0008504
Genomic newborn screening: BabyScreen+ v0.906 ELN Zornitza Stark Classified gene: ELN as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.906 ELN Zornitza Stark Gene: eln has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.905 ELN Zornitza Stark reviewed gene: ELN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: cutis laxa, autosomal dominant 1 MONDO:0007411, supravalvular aortic stenosis MONDO:0008504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.905 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.904 EIF2AK3 Zornitza Stark Gene: eif2ak3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.904 EGR2 Zornitza Stark Gene: egr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.902 EGR2 Zornitza Stark Classified gene: EGR2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.902 EGR2 Zornitza Stark Gene: egr2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.901 EFTUD2 Zornitza Stark Gene: eftud2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.901 EFTUD2 Zornitza Stark Phenotypes for gene: EFTUD2 were changed from Mandibulofacial dysostosis with microcephaly to Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536
Genomic newborn screening: BabyScreen+ v0.900 EFTUD2 Zornitza Stark reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.900 EFL1 Zornitza Stark Gene: efl1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.900 EDNRB Zornitza Stark Gene: ednrb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.900 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.899 EDARADD Zornitza Stark Gene: edaradd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.899 EDARADD Zornitza Stark Phenotypes for gene: EDARADD were changed from Ectodermal dysplasia, hypohidrotic to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
Genomic newborn screening: BabyScreen+ v0.897 EDARADD Zornitza Stark Classified gene: EDARADD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.897 EDARADD Zornitza Stark Gene: edaradd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.896 EDARADD Zornitza Stark reviewed gene: EDARADD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.896 EDAR Zornitza Stark Gene: edar has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.896 EDAR Zornitza Stark Phenotypes for gene: EDAR were changed from Ectodermal dysplasia, hypohidrotic to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
Genomic newborn screening: BabyScreen+ v0.895 EDAR Zornitza Stark Classified gene: EDAR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.895 EDAR Zornitza Stark Gene: edar has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.894 EDAR Zornitza Stark reviewed gene: EDAR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.894 EDA Zornitza Stark Gene: eda has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.894 EDA Zornitza Stark Phenotypes for gene: EDA were changed from Ectodermal dysplasia, hypohidrotic to Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100; Tooth agenesis, selective, X-linked 1 MIM#313500
Genomic newborn screening: BabyScreen+ v0.893 EDA Zornitza Stark Classified gene: EDA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.893 EDA Zornitza Stark Gene: eda has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.892 EDA Zornitza Stark reviewed gene: EDA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100, Tooth agenesis, selective, X-linked 1 MIM#313500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.892 DYSF Zornitza Stark Gene: dysf has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.892 DYSF Zornitza Stark Phenotypes for gene: DYSF were changed from Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, type 2B to Miyoshi muscular dystrophy 1 254130; Muscular dystrophy, limb-girdle, autosomal recessive 2 253601; Myopathy, distal, with anterior tibial onset 606768
Genomic newborn screening: BabyScreen+ v0.891 DYSF Zornitza Stark Classified gene: DYSF as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.891 DYSF Zornitza Stark Gene: dysf has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.890 DYSF Zornitza Stark reviewed gene: DYSF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Miyoshi muscular dystrophy 1 254130, Muscular dystrophy, limb-girdle, autosomal recessive 2 253601, Myopathy, distal, with anterior tibial onset 606768; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 DUOXA2 Zornitza Stark Gene: duoxa2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.890 DUOXA2 Zornitza Stark reviewed gene: DUOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 5, MIM# 274900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 TRIOBP Lilian Downie reviewed gene: TRIOBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:16385457, 16385458; Phenotypes: Deafness, autosomal recessive 28 MIM#609823; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 TRMU Lilian Downie changed review comment from: Onset first 6 months of life
Acute liver failure, transient
Treatment: N-acetylcysteine and L-cysteine, liver transplantation; to: Established gene disease association
Onset first 6 months of life
Acute liver failure, transient
Treatment: N-acetylcysteine and L-cysteine, liver transplantation
Genomic newborn screening: BabyScreen+ v0.890 TRMU Lilian Downie commented on gene: TRMU: Onset first 6 months of life
Acute liver failure, transient
Treatment: N-acetylcysteine and L-cysteine, liver transplantation
Genomic newborn screening: BabyScreen+ v0.890 TRMU Lilian Downie reviewed gene: TRMU: Rating: ; Mode of pathogenicity: None; Publications: PubMed: 19732863, PMID: 36305855; Phenotypes: Liver failure, transient infantile MIM# 613070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 TRPM4 Lilian Downie reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 19726882, PMID: 33381229; Phenotypes: Progressive familial heart block, type IB 604559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.890 TSC1 Lilian Downie reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301399; Phenotypes: Tuberous sclerosis-1 MIM#191100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.890 TSC2 Lilian Downie reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21309039, PMID: 11112665, PMID: 24053983 , PMID: 20301399; Phenotypes: Tuberous sclerosis-2 MIM#613254; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.890 TSEN54 Lilian Downie reviewed gene: TSEN54: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301773; Phenotypes: Pontocerebellar hypoplasia type 2A MIM#277470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 TSR2 Lilian Downie reviewed gene: TSR2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 24942156, 11424144; Phenotypes: Diamond-Blackfan anemia 14 with mandibulofacial dysostosis MIM#300946; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Genomic newborn screening: BabyScreen+ v0.890 TTC21B Lilian Downie reviewed gene: TTC21B: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21258341, PMID: 25492405, PMID: 33547761; Phenotypes: NEPHRONOPHTHISIS, SHORT-RIB THORACIC DYSPLASIA 4 WITH OR WITHOUT POLYDACTYLY; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.890 DUOX2 Zornitza Stark Gene: duox2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.890 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis to Thyroid dyshormonogenesis 6, MIM# 607200
Genomic newborn screening: BabyScreen+ v0.889 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 6, MIM# 607200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.889 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.889 DOCK8 Zornitza Stark Gene: dock8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.889 DOCK8 Zornitza Stark reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive, MIM# 243700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.889 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.888 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.887 DNM2 Zornitza Stark Classified gene: DNM2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.887 DNM2 Zornitza Stark Gene: dnm2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.886 DNAJB6 Zornitza Stark Gene: dnajb6 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.885 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.885 DNAI1 Zornitza Stark Phenotypes for gene: DNAI1 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400
Genomic newborn screening: BabyScreen+ v0.884 DNAI1 Zornitza Stark Classified gene: DNAI1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.884 DNAI1 Zornitza Stark Gene: dnai1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.883 DNAI1 Zornitza Stark reviewed gene: DNAI1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus, MIM# 244400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.883 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.883 DNAH5 Zornitza Stark Phenotypes for gene: DNAH5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644
Genomic newborn screening: BabyScreen+ v0.882 DNAH5 Zornitza Stark Classified gene: DNAH5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.882 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.881 DNAH5 Zornitza Stark reviewed gene: DNAH5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.881 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.881 DNAH11 Zornitza Stark Phenotypes for gene: DNAH11 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884
Genomic newborn screening: BabyScreen+ v0.880 DNAH11 Zornitza Stark Classified gene: DNAH11 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.880 DNAH11 Zornitza Stark Gene: dnah11 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.879 DNAH11 Zornitza Stark reviewed gene: DNAH11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus, MIM#611884; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.879 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.879 DNAAF1 Zornitza Stark Phenotypes for gene: DNAAF1 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 13, MIM# 613193
Genomic newborn screening: BabyScreen+ v0.878 DNAAF1 Zornitza Stark Classified gene: DNAAF1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.878 DNAAF1 Zornitza Stark Gene: dnaaf1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.877 DNAAF1 Zornitza Stark reviewed gene: DNAAF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 13, MIM# 613193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.877 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.877 DMXL2 Zornitza Stark Classified gene: DMXL2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.877 DMXL2 Zornitza Stark Gene: dmxl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.876 DMP1 Zornitza Stark Gene: dmp1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.875 DLL3 Zornitza Stark Gene: dll3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.875 DLL3 Zornitza Stark Phenotypes for gene: DLL3 were changed from Spondylocostal dysostosis, autosomal recessive, 1 to Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300
Genomic newborn screening: BabyScreen+ v0.874 DLL3 Zornitza Stark Classified gene: DLL3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.874 DLL3 Zornitza Stark Gene: dll3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.873 DLL3 Zornitza Stark reviewed gene: DLL3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.873 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.871 DIAPH1 Zornitza Stark Classified gene: DIAPH1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.871 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.870 DFNB59 Zornitza Stark Gene: dfnb59 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.870 DFNB59 Zornitza Stark Phenotypes for gene: DFNB59 were changed from Hearing loss to Deafness, autosomal recessive 59, MIM# 610220
Genomic newborn screening: BabyScreen+ v0.869 DFNB59 Zornitza Stark reviewed gene: DFNB59: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 59, MIM# 610220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.869 DFNA5 Zornitza Stark Gene: dfna5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.868 DFNA5 Zornitza Stark Classified gene: DFNA5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.868 DFNA5 Zornitza Stark Gene: dfna5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.867 SCN8A Zornitza Stark Classified gene: SCN8A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.867 SCN8A Zornitza Stark Gene: scn8a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.866 TYR Zornitza Stark changed review comment from: Treatment is supportive.

For review.; to: Diagnosis is clinical. Treatment is supportive.
Genomic newborn screening: BabyScreen+ v0.866 APC Zornitza Stark Classified gene: APC as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.866 APC Zornitza Stark Gene: apc has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.865 LAMA2 Zornitza Stark Classified gene: LAMA2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.865 LAMA2 Zornitza Stark Gene: lama2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.864 LAMA2 Zornitza Stark changed review comment from: No specific treatment.; to: No specific treatment.
Succinylcholine in induction of anaesthesia because of risk of hyperkalaemia and cardiac conduction abnormalities; statins, cholesterol-lowering medications, because of the risk of muscle damage.
Genomic newborn screening: BabyScreen+ v0.864 DDB2 Zornitza Stark Gene: ddb2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.863 ACVRL1 Zornitza Stark Classified gene: ACVRL1 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.863 ACVRL1 Zornitza Stark Gene: acvrl1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.862 PCBD1 Zornitza Stark changed review comment from: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
; to: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
Genomic newborn screening: BabyScreen+ v0.862 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.862 GFPT1 Zornitza Stark Classified gene: GFPT1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.862 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.861 GFM1 Zornitza Stark Gene: gfm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.860 GFM1 Zornitza Stark Classified gene: GFM1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.860 GFM1 Zornitza Stark Gene: gfm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.859 GFAP Zornitza Stark Gene: gfap has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.858 GFAP Zornitza Stark Classified gene: GFAP as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.858 GFAP Zornitza Stark Gene: gfap has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.857 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.857 DHCR7 Zornitza Stark Classified gene: DHCR7 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.857 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.856 SERPINA1 Zornitza Stark Classified gene: SERPINA1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.856 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.855 SERPINA1 Zornitza Stark reviewed gene: SERPINA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emphysema-cirrhosis, due to AAT deficiency, MIM# 613490; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.855 UROD Zornitza Stark Classified gene: UROD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.855 UROD Zornitza Stark Gene: urod has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.852 DDB2 Zornitza Stark Classified gene: DDB2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.852 DDB2 Zornitza Stark Gene: ddb2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.851 GDAP1 Alison Yeung reviewed gene: GDAP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2K, MIM#607831, Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, MIM#607706, Charcot-Marie-Tooth disease, recessive intermediate, A, MIM#608340, Charcot-Marie-Tooth disease, type 4A, MIM#214400; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.851 DMPK Zornitza Stark Gene: dmpk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.850 DMPK Zornitza Stark Classified gene: DMPK as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.850 DMPK Zornitza Stark Gene: dmpk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.849 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.848 DCX Zornitza Stark Classified gene: DCX as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.848 DCX Zornitza Stark Gene: dcx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.847 DCLRE1C Zornitza Stark Gene: dclre1c has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.846 COL4A5 Zornitza Stark Gene: col4a5 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.844 COL2A1 Zornitza Stark Gene: col2a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.843 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.843 COL5A2 Zornitza Stark Phenotypes for gene: COL5A2 were changed from Ehlers-Danlos syndrome to Ehlers-Danlos syndrome, classic type, 2 MIM#130010
Genomic newborn screening: BabyScreen+ v0.842 COL5A2 Zornitza Stark Classified gene: COL5A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.842 COL5A2 Zornitza Stark Gene: col5a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.841 COL5A2 Zornitza Stark reviewed gene: COL5A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, classic type, 2 MIM#130010; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.841 COL7A1 Zornitza Stark Gene: col7a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.841 COL7A1 Zornitza Stark Phenotypes for gene: COL7A1 were changed from Epidermolysis bullosa dystrophica to EBD inversa, MIM# 226600; EBD, Bart type MIM# 132000 EBD, localisata variant; Epidermolysis bullosa dystrophica, MIM# 131750; Epidermolysis bullosa dystrophica, 226600; Epidermolysis bullosa pruriginosa 604129; Epidermolysis bullosa, pretibial, MIM# 131850; Transient bullous of the newborn 131705
Genomic newborn screening: BabyScreen+ v0.839 COL7A1 Zornitza Stark Classified gene: COL7A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.839 COL7A1 Zornitza Stark Gene: col7a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.838 COL7A1 Zornitza Stark reviewed gene: COL7A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: EBD inversa, MIM# 226600, EBD, Bart type MIM# 132000 EBD, localisata variant, Epidermolysis bullosa dystrophica, MIM# 131750, Epidermolysis bullosa dystrophica, 226600, Epidermolysis bullosa pruriginosa 604129, Epidermolysis bullosa, pretibial, MIM# 131850, Transient bullous of the newborn 131705; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.838 TWIST1 Zornitza Stark Gene: twist1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.838 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from Saethre-Chotzen syndrome to Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Sweeny-Cox syndrome, MIM# 617746; Robinow-Sorauf syndrome, MIM# 180750
Genomic newborn screening: BabyScreen+ v0.836 TWIST1 Zornitza Stark Classified gene: TWIST1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.836 TWIST1 Zornitza Stark Gene: twist1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.835 TWIST1 Zornitza Stark reviewed gene: TWIST1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis 1, MIM# 123100, Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400, Sweeny-Cox syndrome, MIM# 617746, Robinow-Sorauf syndrome, MIM# 180750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.835 TWNK Zornitza Stark Gene: twnk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.833 TWNK Zornitza Stark Classified gene: TWNK as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.833 TWNK Zornitza Stark Gene: twnk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.832 TYMP Zornitza Stark Gene: tymp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.830 TYMP Zornitza Stark Classified gene: TYMP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.830 TYMP Zornitza Stark Gene: tymp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.829 TYR Zornitza Stark Gene: tyr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.827 TYR Zornitza Stark Classified gene: TYR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.827 TYR Zornitza Stark Gene: tyr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.826 UBE2T Zornitza Stark Gene: ube2t has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.825 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.825 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from Ehlers-Danlos syndrome, type I to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000; Fibromuscular dysplasia, multifocal, MIM# 619329
Genomic newborn screening: BabyScreen+ v0.824 COL5A1 Zornitza Stark Classified gene: COL5A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.824 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.823 COL5A1 Zornitza Stark reviewed gene: COL5A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, classic type, 1, MIM# 130000, Fibromuscular dysplasia, multifocal, MIM# 619329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.823 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.821 COL6A3 Zornitza Stark Classified gene: COL6A3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.821 COL6A3 Zornitza Stark Gene: col6a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.820 COL6A2 Zornitza Stark Gene: col6a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.818 COL6A2 Zornitza Stark Classified gene: COL6A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.818 COL6A2 Zornitza Stark Gene: col6a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.817 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.815 COL6A1 Zornitza Stark Classified gene: COL6A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.815 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.814 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.813 TTPA Zornitza Stark Gene: ttpa has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.811 TTR Zornitza Stark Gene: ttr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.811 TTR Zornitza Stark Phenotypes for gene: TTR were changed from Amyloidosis, hereditary, transthyretin-related to Amyloidosis, hereditary, transthyretin-related MIM#105210
Genomic newborn screening: BabyScreen+ v0.809 TTR Zornitza Stark Classified gene: TTR as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.809 TTR Zornitza Stark Gene: ttr has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.808 PDX1 Zornitza Stark Gene: pdx1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.808 PDX1 Zornitza Stark Phenotypes for gene: PDX1 were changed from Pancreatic agenesis, MIM# # 260370 to Pancreatic agenesis, MIM# # 260370
Genomic newborn screening: BabyScreen+ v0.807 PDE4D Zornitza Stark Gene: pde4d has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.807 PDE4D Zornitza Stark Phenotypes for gene: PDE4D were changed from Acrodysostosis 2, with or without hormone resistance to Acrodysostosis 2, with or without hormone resistance, MIM#614613
Genomic newborn screening: BabyScreen+ v0.806 PDE4D Zornitza Stark Classified gene: PDE4D as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.806 PDE4D Zornitza Stark Gene: pde4d has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.805 PCNT Zornitza Stark Gene: pcnt has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.804 PCNT Zornitza Stark Classified gene: PCNT as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.804 PCNT Zornitza Stark Gene: pcnt has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.803 PCDH15 Zornitza Stark Gene: pcdh15 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.803 PCDH15 Zornitza Stark Phenotypes for gene: PCDH15 were changed from Usher syndrome to Usher syndrome, type 1F 602083, Deafness, autosomal recessive 23 609533
Genomic newborn screening: BabyScreen+ v0.802 TTR Lilian Downie reviewed gene: TTR: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301373, PMID: 3032328, PMID: 29972753, PMID: 29972757; Phenotypes: Amyloidosis, hereditary, transthyretin-related MIM#105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.802 PDX1 David Amor reviewed gene: PDX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pancreatic agenesis 1, (Permanent Neonatal Diabetes Mellitus) 260370; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.802 PDE4D David Amor reviewed gene: PDE4D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Acrodysostosis 2, with or without hormone resistance, 614613; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.802 PCDH15 David Amor reviewed gene: PCDH15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Usher syndrome, type 1F 602083, Deafness, autosomal recessive 23 609533; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.802 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.802 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from Osteogenesis imperfecta, type VII to Osteogenesis imperfecta, type VII, MIM# MIM#610682
Genomic newborn screening: BabyScreen+ v0.801 CRTAP Zornitza Stark reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type VII, MIM# MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.801 TWIST1 Lilian Downie reviewed gene: TWIST1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32487807 PMID: 32909287 PMID: 20301368; Phenotypes: Craniosynostosis/Saethre-Chotzen Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.801 CSF2RA Zornitza Stark Gene: csf2ra has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.801 CSF2RA Zornitza Stark Classified gene: CSF2RA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.801 CSF2RA Zornitza Stark Gene: csf2ra has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.800 CSF3R Zornitza Stark Gene: csf3r has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.800 CSF3R Zornitza Stark Phenotypes for gene: CSF3R were changed from Neutropenia, severe congenital, 7, autosomal recessive , MIM#617014; Neutrophilia, hereditary , MIM# 162830 to Neutropenia, severe congenital, 7, autosomal recessive , MIM#617014
Genomic newborn screening: BabyScreen+ v0.798 CSF3R Zornitza Stark reviewed gene: CSF3R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neutropenia, severe congenital, 7, autosomal recessive, MIM# 617014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.798 UBR1 Zornitza Stark Gene: ubr1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.796 UBR1 Zornitza Stark Classified gene: UBR1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.796 UBR1 Zornitza Stark Gene: ubr1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.795 UGT1A1 Zornitza Stark Gene: ugt1a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.793 CSTB Zornitza Stark Gene: cstb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.793 CSTB Zornitza Stark Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800
Genomic newborn screening: BabyScreen+ v0.792 CSTB Zornitza Stark Classified gene: CSTB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.792 CSTB Zornitza Stark Gene: cstb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.791 CSTB Zornitza Stark reviewed gene: CSTB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), MIM# 254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.791 CTC1 Zornitza Stark Gene: ctc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.790 CTC1 Zornitza Stark Classified gene: CTC1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.790 CTC1 Zornitza Stark Gene: ctc1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.789 CTPS1 Zornitza Stark Gene: ctps1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.789 CTSK Zornitza Stark Gene: ctsk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.789 CTSK Zornitza Stark Phenotypes for gene: CTSK were changed from Pycnodysostosis to Pycnodysostosis - MIM#265800
Genomic newborn screening: BabyScreen+ v0.788 CTSK Zornitza Stark Classified gene: CTSK as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.788 CTSK Zornitza Stark Gene: ctsk has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.787 CTSK Zornitza Stark reviewed gene: CTSK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pycnodysostosis - MIM#265800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.787 PCBD1 John Christodoulou changed review comment from: is on the current VCGS newborn screening panel; to: is on the current VCGS newborn screening panel by virtue of phenylalanine being the primary first tier metabolite that is analysed.

Hyperphenylalaninaemia when present in the newborn is transient. There doesn’t appear to be cognitive impairment if untreated, but some individuals develop diabetes and/or mild hypomagnesaemia later in adolescence. There does not appear to be any evidence that any treatments in infancy would have an effect on these two late effects. See: PMID: 32456656

So, I think we can take this one off the list.
Genomic newborn screening: BabyScreen+ v0.787 CUL7 Zornitza Stark Gene: cul7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.786 CUL7 Zornitza Stark Classified gene: CUL7 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.786 CUL7 Zornitza Stark Gene: cul7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.785 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.785 CYBA Zornitza Stark Gene: cyba has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.785 CYBA Zornitza Stark reviewed gene: CYBA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chronic granulomatous disease 4, autosomal recessive, MIM# 233690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.785 CYBB Zornitza Stark Gene: cybb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.785 CYP4F22 Zornitza Stark Gene: cyp4f22 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.785 CYP4F22 Zornitza Stark Phenotypes for gene: CYP4F22 were changed from Ichthyosis, congenital, autosomal recessive to Ichthyosis, congenital, autosomal recessive 5, MIM# 604777
Genomic newborn screening: BabyScreen+ v0.784 CYP4F22 Zornitza Stark Classified gene: CYP4F22 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.784 CYP4F22 Zornitza Stark Gene: cyp4f22 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.783 CYP4F22 Zornitza Stark reviewed gene: CYP4F22: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, congenital, autosomal recessive 5, MIM# 604777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.783 MMAB Zornitza Stark Gene: mmab has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.783 IVD Zornitza Stark Gene: ivd has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.783 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.782 G6PC3 Zornitza Stark Gene: g6pc3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.782 CREBBP Zornitza Stark Gene: crebbp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.781 CREBBP Zornitza Stark Classified gene: CREBBP as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.781 CREBBP Zornitza Stark Gene: crebbp has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.780 COL1A2 Zornitza Stark Gene: col1a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.780 COL1A2 Zornitza Stark Phenotypes for gene: COL1A2 were changed from Osteogenesis imperfecta, type II to Osteogenesis imperfecta, type II , MIM#166210
Genomic newborn screening: BabyScreen+ v0.779 COL1A2 Zornitza Stark reviewed gene: COL1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type II , MIM#166210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.779 COL1A1 Zornitza Stark Gene: col1a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.779 COL1A1 Zornitza Stark Phenotypes for gene: COL1A1 were changed from Osteogenesis imperfecta, type I to Osteogenesis imperfecta, type I, MIM#166200
Genomic newborn screening: BabyScreen+ v0.778 COL1A1 Zornitza Stark reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type I MIM#166200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.778 COL17A1 Zornitza Stark Gene: col17a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.778 COL17A1 Zornitza Stark Phenotypes for gene: COL17A1 were changed from Epidermolysis bullosa, junctional, non-Herlitz type to Epidermolysis bullosa, junctional 4, intermediate MIM#619787
Genomic newborn screening: BabyScreen+ v0.777 COL17A1 Zornitza Stark Classified gene: COL17A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.777 COL17A1 Zornitza Stark Gene: col17a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.776 COL17A1 Zornitza Stark reviewed gene: COL17A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epidermolysis bullosa, junctional 4, intermediate MIM#619787; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.776 PHYH Zornitza Stark Gene: phyh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.775 PHYH Zornitza Stark Classified gene: PHYH as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.775 PHYH Zornitza Stark Gene: phyh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.774 PHKG2 Zornitza Stark Gene: phkg2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.773 PHKB Zornitza Stark Gene: phkb has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.773 PHKB Zornitza Stark Phenotypes for gene: PHKB were changed from Phosphorylase kinase deficiency to Phosphorylase kinase deficiency of liver and muscle, autosomal recessive 261750; Glycogen storage disease IXb, MONDO:0009868
Genomic newborn screening: BabyScreen+ v0.772 PHKA2 Zornitza Stark Gene: phka2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.770 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.770 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.770 PFKM Zornitza Stark Gene: pfkm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.768 PFKM Zornitza Stark Classified gene: PFKM as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.768 PFKM Zornitza Stark Gene: pfkm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.767 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.767 PEX7 Zornitza Stark Phenotypes for gene: PEX7 were changed from Rhizomelic chondrodysplasia punctata; Refsum disease to Peroxisome biogenesis disorder 9B, MIM# 614879; Rhizomelic chondrodysplasia punctata, type 1, MIM# 215100
Genomic newborn screening: BabyScreen+ v0.766 PEX7 Zornitza Stark Classified gene: PEX7 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.766 PEX7 Zornitza Stark Gene: pex7 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.765 PEX6 Zornitza Stark Gene: pex6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.765 PEX6 Zornitza Stark Phenotypes for gene: PEX6 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 4A (Zellweger) (MIM#614862)
Genomic newborn screening: BabyScreen+ v0.764 PEX6 Zornitza Stark Classified gene: PEX6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.764 PEX6 Zornitza Stark Gene: pex6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.763 PEX5 Zornitza Stark Gene: pex5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.763 PEX5 Zornitza Stark Phenotypes for gene: PEX5 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 10A (Zellweger) 614882
Genomic newborn screening: BabyScreen+ v0.762 PEX5 Zornitza Stark Classified gene: PEX5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.762 PEX5 Zornitza Stark Gene: pex5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.761 PEX3 Zornitza Stark Gene: pex3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.761 PEX3 Zornitza Stark Phenotypes for gene: PEX3 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 10A (Zellweger) 614882
Genomic newborn screening: BabyScreen+ v0.760 PEX3 Zornitza Stark Classified gene: PEX3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.760 PEX3 Zornitza Stark Gene: pex3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.759 PEX26 Zornitza Stark Gene: pex26 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.759 PEX26 Zornitza Stark Phenotypes for gene: PEX26 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 7A (Zellweger) MIM#614872
Genomic newborn screening: BabyScreen+ v0.758 PEX26 Zornitza Stark Classified gene: PEX26 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.758 PEX26 Zornitza Stark Gene: pex26 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.757 PEX2 Zornitza Stark Gene: pex2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.757 PEX2 Zornitza Stark Phenotypes for gene: PEX2 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 5A (Zellweger) MIM#614866
Genomic newborn screening: BabyScreen+ v0.756 PEX2 Zornitza Stark Classified gene: PEX2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.756 PEX2 Zornitza Stark Gene: pex2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.755 PEX13 Zornitza Stark Gene: pex13 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.755 PEX13 Zornitza Stark Phenotypes for gene: PEX13 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 11A (Zellweger) (MIM#614883)
Genomic newborn screening: BabyScreen+ v0.754 PEX13 Zornitza Stark Classified gene: PEX13 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.754 PEX13 Zornitza Stark Gene: pex13 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.753 PEX12 Zornitza Stark Gene: pex12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.753 PEX12 Zornitza Stark Phenotypes for gene: PEX12 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 3A (Zellweger) (MIM#614859)
Genomic newborn screening: BabyScreen+ v0.752 PEX12 Zornitza Stark Classified gene: PEX12 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.752 PEX12 Zornitza Stark Gene: pex12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.751 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.751 PEX10 Zornitza Stark Phenotypes for gene: PEX10 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 6A (Zellweger) (MIM#614870)
Genomic newborn screening: BabyScreen+ v0.750 PEX10 Zornitza Stark Classified gene: PEX10 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.750 PEX10 Zornitza Stark Gene: pex10 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.749 PAX6 Zornitza Stark Gene: pax6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.748 PAX6 Zornitza Stark Classified gene: PAX6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.748 PAX6 Zornitza Stark Gene: pax6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.747 PAX3 Zornitza Stark Gene: pax3 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.746 PANK2 Zornitza Stark Gene: pank2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.745 PANK2 Zornitza Stark Classified gene: PANK2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.745 PANK2 Zornitza Stark Gene: pank2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.744 PAK3 Zornitza Stark Gene: pak3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.743 PAK3 Zornitza Stark Classified gene: PAK3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.743 PAK3 Zornitza Stark Gene: pak3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.742 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.741 P2RY12 Zornitza Stark Classified gene: P2RY12 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.741 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.740 PEX1 Zornitza Stark Gene: pex1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.740 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from Zellweger syndrome to Peroxisome biogenesis disorder 1A (Zellweger), MIM# 214100
Genomic newborn screening: BabyScreen+ v0.739 PEX1 Zornitza Stark Classified gene: PEX1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.739 PEX1 Zornitza Stark Gene: pex1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.738 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.736 PDHA1 Zornitza Stark Gene: pdha1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.734 PC Zornitza Stark Gene: pc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.732 PAX8 Zornitza Stark Gene: pax8 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.732 PAX8 Zornitza Stark Phenotypes for gene: PAX8 were changed from Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia to Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700
Genomic newborn screening: BabyScreen+ v0.730 SLC16A2 Zornitza Stark Classified gene: SLC16A2 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.730 SLC16A2 Zornitza Stark Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.729 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.729 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.727 UROD Zornitza Stark Gene: urod has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.725 SI Zornitza Stark Tag for review was removed from gene: SI.
Genomic newborn screening: BabyScreen+ v0.725 SFTPC Zornitza Stark Classified gene: SFTPC as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.725 SFTPC Zornitza Stark Gene: sftpc has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.724 SCN3A Zornitza Stark Classified gene: SCN3A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.724 SCN3A Zornitza Stark Gene: scn3a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.723 SCN2A Zornitza Stark Classified gene: SCN2A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.723 SCN2A Zornitza Stark Gene: scn2a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.722 SCN1A Zornitza Stark Classified gene: SCN1A as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.722 SCN1A Zornitza Stark Gene: scn1a has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.721 PCBD1 Zornitza Stark changed review comment from: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.

For review; to: Well established gene-disease association.

Presents in the neonatal period: characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported. Patients may also develop hypomagnesemia and non-autoimmune diabetes mellitus during puberty.
Genomic newborn screening: BabyScreen+ v0.721 MYO6 Zornitza Stark Phenotypes for gene: MYO6 were changed from Deafness, autosomal dominant 22, MIM# 606346; Deafness, autosomal recessive 37, MIM# 607821 to Deafness, autosomal recessive 37, MIM# 607821
Genomic newborn screening: BabyScreen+ v0.719 PHYH John Christodoulou reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: retinitis pigmentosa with night blindness, cataracts, polyneuropathy including sensory disturbances, cerebellar ataxia, anosmia, progressive hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PHKG2 John Christodoulou reviewed gene: PHKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30659246, https://www.ncbi.nlm.nih.gov/books/NBK55061/#gsd9.Summary; Phenotypes: hepatomegaly, hypotonia, growth retardation, hypoglycaemia, fasting ketosis, cirrhosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PHKB John Christodoulou reviewed gene: PHKB: Rating: GREEN; Mode of pathogenicity: None; Publications: https://www.ncbi.nlm.nih.gov/books/NBK55061/#gsd9.Summary; Phenotypes: marked hepatomegaly, hypoglycaemia, short stature, fasting ketosis, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PHKA2 John Christodoulou reviewed gene: PHKA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30659246; Phenotypes: hepatomegaly, short stature, liver dysfunction, hypoglycaemia, hyperuricaemia, hyperlipidemia, fasting ketosis, mild motor delay; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.719 PGM1 John Christodoulou reviewed gene: PGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32681750; Phenotypes: cleft lip, bifid uvula, hepatopathy, intermittent hypoglycemia, short stature, exercise intolerance, increased serum creatine kinase, rhabdomyolysis, dilated cardiomyopathy, hypogonadotropic hypogonadism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PFKM John Christodoulou reviewed gene: PFKM: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 7550225; Phenotypes: rhabdomyolysis, myopathy, exercise intolerance, gout, haemolysis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PDHX John Christodoulou reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20002125, PMID: 33092611; Phenotypes: ID, hypotonia, lactic acidosis, seizures, dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 PDHA1 John Christodoulou reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: lactic acidosis, porencephaly, ID, seizures, dystonia; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Genomic newborn screening: BabyScreen+ v0.719 PC John Christodoulou reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301764; Phenotypes: lactic acidosis, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 OXCT1 John Christodoulou reviewed gene: OXCT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30799594, PMID: 20652411; Phenotypes: ketoacidosis, hypoglycaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 NPC2 John Christodoulou reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29625568, PMID: 30732631; Phenotypes: cholestatic jaundice in infancy, gaze palsy, ID, dystonia, progressive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 MLYCD John Christodoulou reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 28781843, PMID: 20549361; Phenotypes: hypoglycaemia, metabolic acidosis, cardiomyopathy, ID, seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 MAN2B1 John Christodoulou reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31222755, PMID: 31241255; Phenotypes: ID, coarse facial features, deafness, dysostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.719 SLC17A5 Seb Lunke Gene: slc17a5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.719 SLC17A5 Seb Lunke Phenotypes for gene: SLC17A5 were changed from Sialic acid storage disorder, infantile to Sialic acid storage disorder, infantile, MIM# 269920
Genomic newborn screening: BabyScreen+ v0.718 SLC17A5 Seb Lunke Classified gene: SLC17A5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.718 SLC17A5 Seb Lunke Gene: slc17a5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.717 SLC17A5 Seb Lunke reviewed gene: SLC17A5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Sialic acid storage disorder, infantile, MIM# 269920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.717 SLC16A2 Seb Lunke Gene: slc16a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.716 SLC16A2 Seb Lunke Classified gene: SLC16A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.716 SLC16A2 Seb Lunke Added comment: Comment on list classification: Not eligible now but have to check back on trial later
Genomic newborn screening: BabyScreen+ v0.716 SLC16A2 Seb Lunke Gene: slc16a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.715 SLC12A6 Seb Lunke Gene: slc12a6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.715 SLC12A6 Seb Lunke Phenotypes for gene: SLC12A6 were changed from Agenesis of the corpus callosum with peripheral neuropathy to Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800
Genomic newborn screening: BabyScreen+ v0.714 SLC12A6 Seb Lunke Classified gene: SLC12A6 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.714 SLC12A6 Seb Lunke Gene: slc12a6 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.713 SLC12A6 Seb Lunke reviewed gene: SLC12A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.713 SLC12A3 Seb Lunke Gene: slc12a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.712 SLC12A3 Seb Lunke Classified gene: SLC12A3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.712 SLC12A3 Seb Lunke Gene: slc12a3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.711 SLC12A1 Seb Lunke Gene: slc12a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.710 SKI Seb Lunke Gene: ski has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.709 SKI Seb Lunke Classified gene: SKI as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.709 SKI Seb Lunke Gene: ski has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.708 SIX3 Seb Lunke Marked gene: SIX3 as ready
Genomic newborn screening: BabyScreen+ v0.708 SIX3 Seb Lunke Gene: six3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.708 SIX3 Seb Lunke Phenotypes for gene: SIX3 were changed from Holoprosencephaly-2 to Holoprosencephaly 2, MIM# 157170
Genomic newborn screening: BabyScreen+ v0.707 SIX3 Seb Lunke Classified gene: SIX3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.707 SIX3 Seb Lunke Gene: six3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.706 SIX3 Seb Lunke reviewed gene: SIX3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 2, MIM# 157170; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.706 SIX1 Seb Lunke Marked gene: SIX1 as ready
Genomic newborn screening: BabyScreen+ v0.706 SIX1 Seb Lunke Gene: six1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.706 SIX1 Seb Lunke Phenotypes for gene: SIX1 were changed from Branchiootorenal syndrome to Branchiootic syndrome 3, MIM# 608389
Genomic newborn screening: BabyScreen+ v0.705 SIX1 Seb Lunke Classified gene: SIX1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.705 SIX1 Seb Lunke Gene: six1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.704 SIX1 Seb Lunke reviewed gene: SIX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiootic syndrome 3, MIM# 608389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genomic newborn screening: BabyScreen+ v0.704 SIL1 Seb Lunke Marked gene: SIL1 as ready
Genomic newborn screening: BabyScreen+ v0.704 SIL1 Seb Lunke Gene: sil1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.704 SIL1 Seb Lunke Phenotypes for gene: SIL1 were changed from Marinesco-Sjogren syndrome to Marinesco-Sjogren syndrome, MIM#248800
Genomic newborn screening: BabyScreen+ v0.703 SIL1 Seb Lunke Classified gene: SIL1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.703 SIL1 Seb Lunke Gene: sil1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.702 SIL1 Seb Lunke reviewed gene: SIL1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Marinesco-Sjogren syndrome, MIM#248800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.702 SI Seb Lunke Marked gene: SI as ready
Genomic newborn screening: BabyScreen+ v0.702 SI Seb Lunke Gene: si has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.702 SI Seb Lunke Tag for review tag was added to gene: SI.
Genomic newborn screening: BabyScreen+ v0.702 SI Seb Lunke reviewed gene: SI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sucrase-isomaltase deficiency, congenital, MIM# 222900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.702 SHH Seb Lunke Gene: shh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.701 SHH Seb Lunke Classified gene: SHH as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.701 SHH Seb Lunke Gene: shh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.700 SHANK3 Seb Lunke Gene: shank3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.700 SHANK3 Seb Lunke Classified gene: SHANK3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.700 SHANK3 Seb Lunke Gene: shank3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.699 SH3TC2 Seb Lunke Gene: sh3tc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.698 SH3TC2 Seb Lunke Classified gene: SH3TC2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.698 SH3TC2 Seb Lunke Gene: sh3tc2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.697 SH2D1A Seb Lunke Gene: sh2d1a has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.695 SGSH Seb Lunke Gene: sgsh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.695 SGSH Seb Lunke Phenotypes for gene: SGSH were changed from Mucopolysaccharidisis type IIIA (Sanfilippo A) to Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900
Genomic newborn screening: BabyScreen+ v0.694 SGSH Seb Lunke Classified gene: SGSH as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.694 SGSH Seb Lunke Gene: sgsh has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.693 SGSH Seb Lunke reviewed gene: SGSH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.693 SGCB Seb Lunke Gene: sgcb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.693 SGCG Seb Lunke Gene: sgcg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.693 SGCB Seb Lunke Phenotypes for gene: SGCB were changed from Muscular dystrophy, limb-girdle, type 2E to Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286
Genomic newborn screening: BabyScreen+ v0.692 SGCD Seb Lunke Gene: sgcd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.692 SGCG Seb Lunke Phenotypes for gene: SGCG were changed from Muscular dystrophy, limb-girdle, type 2C to Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700
Genomic newborn screening: BabyScreen+ v0.691 SGCB Seb Lunke Classified gene: SGCB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.691 SGCB Seb Lunke Gene: sgcb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.690 SGCD Seb Lunke Classified gene: SGCD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.690 SGCD Seb Lunke Gene: sgcd has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.689 SGCG Seb Lunke Classified gene: SGCG as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.689 SGCG Seb Lunke Gene: sgcg has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.688 SGCG Seb Lunke reviewed gene: SGCG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.688 SGCD Seb Lunke reviewed gene: SGCD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.688 SGCB Seb Lunke reviewed gene: SGCB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.688 SGCA Seb Lunke Gene: sgca has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.688 SGCA Seb Lunke Phenotypes for gene: SGCA were changed from Muscular dystrophy, limb-girdle, type 2D to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099
Genomic newborn screening: BabyScreen+ v0.687 SGCA Seb Lunke Classified gene: SGCA as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.687 SGCA Seb Lunke Gene: sgca has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.686 SGCA Seb Lunke reviewed gene: SGCA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.686 COL13A1 Zornitza Stark Gene: col13a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.686 COL11A2 Zornitza Stark Classified gene: COL11A2 as Green List (high evidence)
Genomic newborn screening: BabyScreen+ v0.686 COL11A2 Zornitza Stark Gene: col11a2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.685 COL11A2 Zornitza Stark Gene: col11a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.685 COL11A2 Zornitza Stark Phenotypes for gene: COL11A2 were changed from Otospondylomegaepiphyseal dysplasia to Deafness, autosomal recessive 53, MIM# 609706
Genomic newborn screening: BabyScreen+ v0.683 COL11A2 Zornitza Stark Classified gene: COL11A2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.683 COL11A2 Zornitza Stark Gene: col11a2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.682 COL11A2 Zornitza Stark reviewed gene: COL11A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 53, MIM# 609706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.682 COL11A1 Zornitza Stark Gene: col11a1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.681 COG5 Zornitza Stark Gene: cog5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.680 COG5 Zornitza Stark Classified gene: COG5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.680 COG5 Zornitza Stark Gene: cog5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.679 OXCT1 Zornitza Stark Gene: oxct1 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.679 OTOGL Zornitza Stark Gene: otogl has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.679 OTOGL Zornitza Stark Phenotypes for gene: OTOGL were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 84B, MIM# 614944
Genomic newborn screening: BabyScreen+ v0.678 OTOGL Zornitza Stark reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 84B, MIM# 614944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.678 OTOF Zornitza Stark Gene: otof has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.678 OTOF Zornitza Stark Phenotypes for gene: OTOF were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 9, MIM#601071
Genomic newborn screening: BabyScreen+ v0.677 OTOA Zornitza Stark Gene: otoa has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.677 OTOA Zornitza Stark Phenotypes for gene: OTOA were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 22, MIM#607039
Genomic newborn screening: BabyScreen+ v0.676 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.676 OSTM1 Zornitza Stark Gene: ostm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.676 OSTM1 Zornitza Stark Phenotypes for gene: OSTM1 were changed from Osteopetrosis to Osteopetrosis, autosomal recessive 5, MIM#259720
Genomic newborn screening: BabyScreen+ v0.674 OSTM1 Zornitza Stark Classified gene: OSTM1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.674 OSTM1 Zornitza Stark Gene: ostm1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.673 DPAGT1 Zornitza Stark changed review comment from: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.; to: Bi-allelic variants cause either multi-system CDG or congenital myasthenia gravis.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.
Genomic newborn screening: BabyScreen+ v0.673 UMOD Zornitza Stark Gene: umod has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.671 UMOD Zornitza Stark Classified gene: UMOD as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.671 UMOD Zornitza Stark Gene: umod has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.670 OTOGL David Amor reviewed gene: OTOGL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 614944, Deafness, autosomal recessive 84B; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.670 OTOF David Amor reviewed gene: OTOF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 601071, Auditory neuropathy, autosomal recessive, 1, AND Deafness, autosomal recessive 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.670 OTOA David Amor changed review comment from: Gene-disease association: strong. Note that large deletions are relatively common - will we detect by WGS?

Severity: moderate to severe prelingual sensorineural recessive deafness

Age of onset: congenital

Non-molecular confirmatory testing: audiology

Treatment: symptomatic only therefore exclude; to: Gene-disease association: strong. Note that large deletions are relatively common - will we detect by WGS?

Severity: moderate to severe prelingual sensorineural recessive deafness

Age of onset: congenital

Non-molecular confirmatory testing: audiology

Treatment: HA, CI.
Genomic newborn screening: BabyScreen+ v0.670 OTOA David Amor reviewed gene: OTOA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 607039, Deafness, autosomal recessive 22; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.670 OSTM1 David Amor reviewed gene: OSTM1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34011644; Phenotypes: 259720 Osteopetrosis, autosomal recessive 5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.670 UNC13D Zornitza Stark Gene: unc13d has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.669 MEN1 Zornitza Stark Classified gene: MEN1 as Amber List (moderate evidence)
Genomic newborn screening: BabyScreen+ v0.669 MEN1 Zornitza Stark Gene: men1 has been classified as Amber List (Moderate Evidence).
Genomic newborn screening: BabyScreen+ v0.668 MEN1 Zornitza Stark Classified gene: MEN1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.668 MEN1 Zornitza Stark Gene: men1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.667 MAGI2 Zornitza Stark Gene: magi2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.665 MAGI2 Zornitza Stark Classified gene: MAGI2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.665 MAGI2 Zornitza Stark Gene: magi2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.664 LRP5 Zornitza Stark changed review comment from: Gene is associated with multiple phenotypes.

Bisphosphanate is used to treat osteoporosis. Onset of bone fragility is in childhood.

Non-genetic confirmatory testing: skeletal survey, but uncertain at what stage abnormalities would appear.

For review.; to: Gene is associated with multiple phenotypes.

Bisphosphanate is used to treat osteoporosis. Onset of bone fragility is in childhood.

Non-genetic confirmatory testing: skeletal survey, but uncertain at what stage abnormalities would appear.

For review: only include bi-allelic disease.
Genomic newborn screening: BabyScreen+ v0.664 FUCA1 Zornitza Stark changed review comment from: Non-genetic confirmatory testing: fucosidase activity in serum or plasma

For review regarding utility of BMT.; to: Non-genetic confirmatory testing: fucosidase activity in serum or plasma

For review regarding utility of BMT: include, uncertain if pre-symptomatic BMT may have better outcomes than currently reported.
Genomic newborn screening: BabyScreen+ v0.664 ETFB Zornitza Stark changed review comment from: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis; to: Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates

Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis

Predominantly neonatal onset.
Genomic newborn screening: BabyScreen+ v0.664 LRP4 Zornitza Stark Classified gene: LRP4 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.664 LRP4 Zornitza Stark Gene: lrp4 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.662 LDLR Zornitza Stark changed review comment from: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.; to: ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.

Include bi-allelic disease in gNBS. Continue considering if and when mono-allelic disease should be included.
Genomic newborn screening: BabyScreen+ v0.662 GATA4 Zornitza Stark Gene: gata4 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.661 FLAD1 Zornitza Stark changed review comment from: Well established gene-disease association, more than 10 families reported.

The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment.

For discussion. Included as a treatable disorder in rx-genes.

Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis,; to: Well established gene-disease association, more than 10 families reported.

The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment.

Included as a treatable disorder in rx-genes.

Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis,
Genomic newborn screening: BabyScreen+ v0.661 DPAGT1 Zornitza Stark changed review comment from: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

For review.; to: Bi-allelic variants cause either multi-system CDG or congenital myasthenia graves.

Difficult to predict phenotype from genotype but MG may be responsive to treatment.

Phenotype may already be apparent in newborn period so clinical correlation possible.
Genomic newborn screening: BabyScreen+ v0.661 COQ8B Zornitza Stark Classified gene: COQ8B as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.661 COQ8B Zornitza Stark Gene: coq8b has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.660 UNC13D Lilian Downie reviewed gene: UNC13D: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301617; Phenotypes: Hemophagocytic lymphohistiocytosis MIM#608898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.660 COCH Zornitza Stark Gene: coch has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.660 COCH Zornitza Stark Phenotypes for gene: COCH were changed from Deafness, autosomal dominant 9, MIM# 601369; Deafness, autosomal recessive 110, MIM# 618094 to Deafness, autosomal recessive 110, MIM# 618094
Genomic newborn screening: BabyScreen+ v0.658 COCH Zornitza Stark reviewed gene: COCH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 110, MIM# 618094; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.658 CNGB3 Zornitza Stark Gene: cngb3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.658 CNGB3 Zornitza Stark Phenotypes for gene: CNGB3 were changed from Achromatopsia-3 to Achromatopsia 3, MIM# 262300
Genomic newborn screening: BabyScreen+ v0.657 CNGB3 Zornitza Stark Classified gene: CNGB3 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.657 CNGB3 Zornitza Stark Gene: cngb3 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.656 CNGB3 Zornitza Stark reviewed gene: CNGB3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Achromatopsia 3, MIM# 262300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.656 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.655 CLRN1 Zornitza Stark Classified gene: CLRN1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.655 CLRN1 Zornitza Stark Gene: clrn1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.654 CLPP Zornitza Stark Gene: clpp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.654 CLDN19 Zornitza Stark Gene: cldn19 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.654 CLDN19 Zornitza Stark Phenotypes for gene: CLDN19 were changed from Hypomagnesemia 5, renal, with ocular involvement to Deafness, autosomal recessive 116 MIM#619093
Genomic newborn screening: BabyScreen+ v0.653 CLDN19 Zornitza Stark Classified gene: CLDN19 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.653 CLDN19 Zornitza Stark Gene: cldn19 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.652 CLDN19 Zornitza Stark reviewed gene: CLDN19: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 116 MIM#619093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.652 CLDN14 Zornitza Stark Gene: cldn14 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.652 CLDN14 Zornitza Stark Phenotypes for gene: CLDN14 were changed from Hearing loss, non-syndromic, autosomal recessive to Deafness, autosomal recessive 29, MIM# 614035
Genomic newborn screening: BabyScreen+ v0.651 CLDN14 Zornitza Stark reviewed gene: CLDN14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 29, MIM# 614035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.651 SFTPC Seb Lunke Gene: sftpc has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.650 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.650 CLCN7 Zornitza Stark reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 4, MIM# 611490; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.650 CEP78 Zornitza Stark Gene: cep78 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.649 CEP78 Zornitza Stark Classified gene: CEP78 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.649 CEP78 Zornitza Stark Gene: cep78 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.648 SFTPB Seb Lunke Gene: sftpb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.647 SFTPB Seb Lunke Classified gene: SFTPB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.647 SFTPB Seb Lunke Gene: sftpb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.646 SETX Seb Lunke Gene: setx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.646 SETX Seb Lunke Phenotypes for gene: SETX were changed from Ataxia-ocular apraxia 2 to Spinocerebellar ataxia, autosomal recessive 1, 606002
Genomic newborn screening: BabyScreen+ v0.645 SETX Seb Lunke Classified gene: SETX as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.645 SETX Seb Lunke Gene: setx has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.644 SETX Seb Lunke reviewed gene: SETX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 1, 606002; Mode of inheritance: None
Genomic newborn screening: BabyScreen+ v0.644 SETBP1 Seb Lunke Gene: setbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.643 SETBP1 Seb Lunke Classified gene: SETBP1 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.643 SETBP1 Seb Lunke Gene: setbp1 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.642 CLCN5 Zornitza Stark Gene: clcn5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.641 CLCN5 Zornitza Stark Classified gene: CLCN5 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.641 CLCN5 Zornitza Stark Gene: clcn5 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.640 CIB2 Zornitza Stark Gene: cib2 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.640 CIB2 Zornitza Stark reviewed gene: CIB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 48, MIM# 609439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Genomic newborn screening: BabyScreen+ v0.640 CHM Zornitza Stark Gene: chm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.639 CHM Zornitza Stark Classified gene: CHM as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.639 CHM Zornitza Stark Gene: chm has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.638 CHKB Zornitza Stark Gene: chkb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.637 CHKB Zornitza Stark Classified gene: CHKB as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.637 CHKB Zornitza Stark Gene: chkb has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.636 CHD2 Zornitza Stark Gene: chd2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.635 CHD2 Zornitza Stark Classified gene: CHD2 as Red List (low evidence)
Genomic newborn screening: BabyScreen+ v0.635 CHD2 Zornitza Stark Gene: chd2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.634 CFP Zornitza Stark Gene: cfp has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v0.634 CFL2 Zornitza Stark Gene: cfl2 has been classified as Red List (Low Evidence).
Genomic newborn screening: BabyScreen+ v0.634 CFL2 Zornitza Stark Phenotypes for gene: CFL2 were changed from Nemaline myopathy to Nemaline myopathy 7, autosomal recessive, MIM# 610687
Genomic newborn screening: BabyScreen+ v0.633 CFL2 Zornitza Stark Classified gene: CFL2 as Red List (low evidence)