| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genomic newborn screening: BabyScreen+ v1.110 | TSHR | Zornitza Stark Phenotypes for gene: TSHR were changed from Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200; HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM to Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v1.74 | LAT |
Zornitza Stark gene: LAT was added gene: LAT was added to BabyScreen+ newborn screening. Sources: Expert list treatable, immunological tags were added to gene: LAT. Mode of inheritance for gene: LAT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LAT were set to Immunodeficiency 52, MIM# 617514 Review for gene: LAT was set to GREEN Added comment: Established gene-disease association. SCID-like presentation. Treatment: BMT Non-genetic confirmatory testing: yes Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v1.56 | ERCC4 | Zornitza Stark Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, MIM# 278760; Xeroderma pigmentosum; Fanconi anaemia, complementation group Q, MIM# 615272 to Fanconi anemia, complementation group Q, MIM# 615272 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v1.54 | ERCC4 | Zornitza Stark reviewed gene: ERCC4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group Q, MIM# 615272; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v1.31 | C2 |
Zornitza Stark gene: C2 was added gene: C2 was added to BabyScreen+ newborn screening. Sources: Expert list Mode of inheritance for gene: C2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C2 were set to 31421540 Phenotypes for gene: C2 were set to C2 deficiency, MIM# 217000 Review for gene: C2 was set to GREEN Added comment: Established gene-disease association. Can present with severe early infections in infancy/childhood. Later manifestations include autoimmune phenomena. Treatment: pneumococcal, meningococcal, haemophilus influenzae vaccines Non-genetic confirmatory tests: complement levels Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v1.20 | IGHM | Zornitza Stark changed review comment from: RefSeq annotation issues.; to: RefSeq annotation issues. Specific rescue loop built to capture variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v1.15 | IGHM | Zornitza Stark commented on gene: IGHM: RefSeq annotation issues. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ 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+ v0.2172 | 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+ v0.2170 | 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+ v0.2158 | 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+ v0.2141 | 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+ v0.2134 | 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+ v0.2133 | 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+ v0.2131 | 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+ v0.2130 | 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+ v0.2129 | 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+ v0.2126 | CASQ2 |
Zornitza Stark changed review comment from: Well established gene-disease association. ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided. 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. ; to: Well established gene-disease association. ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided. 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. Reviewed with paediatric cardiologist: variable penetrance and age of onset. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.2123 | 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+ v0.2072 | SOX3 | Zornitza Stark reviewed gene: SOX3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Panhypopituitarism, X-linked MIM#312000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.2072 | STAT1 | Zornitza Stark Marked gene: STAT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.2072 | STAT1 | Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.2072 | STAT1 | Zornitza Stark Mode of inheritance for gene: STAT1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 Tag treatable tag was added to gene: STAT1. Tag immunological tag was added to gene: STAT1. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.2063 | SARS |
Lilian Downie gene: SARS was added gene: SARS was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SARS were set to PMID:34570399, PMID: 34194004 Phenotypes for gene: SARS were set to Neurodevelopmental disorder with microcephaly, ataxia, and seizures MIM#617709 Review for gene: SARS was set to RED Added comment: developmental delay, deafness, cardiomyopathy, epilepsy, and severe febrile decompensations Rx serine supplementation - limited evidence and sounds supportive only Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.2063 | SERPING1 |
Lilian Downie gene: SERPING1 was added gene: SERPING1 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: SERPING1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SERPING1 were set to PMID: 32898710 Phenotypes for gene: SERPING1 were set to Angioedema, hereditary, 1 and 2 MIM#106100 Review for gene: SERPING1 was set to RED Added comment: episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. Age of onset not typically <5 Treatment Purified C1 inhibitor concentrate (Cinryze, Berinert, HAEGARDA, or Ruconest), Ecallantide (Kalbitor), Icatibant (Firazyr), Lanadelumab, Orladeyo (berotralstat), FFP or solvent-detergent treated plasma, antisense oligonucleotide treatment (donidalorsen) 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 | 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 | 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 | TBL1X |
Lilian Downie gene: TBL1X was added gene: TBL1X was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TBL1X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: TBL1X were set to PMID: 27603907 Phenotypes for gene: TBL1X were set to Hypothyroidism, congenital, nongoitrous, 8 MIM#301033 Review for gene: TBL1X was set to GREEN Added comment: Small thyroid gland Detected on newborn screening Can affect carrier females but more mildly Association with deafness Rx thyroxine Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.2052 | 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+ v0.2044 | 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+ v0.2028 | MNX1 |
Zornitza Stark gene: MNX1 was added gene: MNX1 was added to Baby Screen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: MNX1. Mode of inheritance for gene: MNX1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MNX1 were set to 36586106 Phenotypes for gene: MNX1 were set to Permanent neonatal diabetes mellitus, MONDO:0100164, MNX1-related Review for gene: MNX1 was set to GREEN Added comment: Three unrelated families reported. Presentation is in newborn period. Treatment: insulin. Non-genetic confirmatory testing: glucose tolerance test, hemoglobin A1C, insulin level, glucose level Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.2011 | IRS4 |
Zornitza Stark gene: IRS4 was added gene: IRS4 was added to Baby Screen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: IRS4. Mode of inheritance for gene: IRS4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: IRS4 were set to 30061370 Phenotypes for gene: IRS4 were set to Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035 Review for gene: IRS4 was set to GREEN Added comment: Nongoitrous congenital hypothyroidism-9 (CHNG9) is characterized by a small thyroid gland with low free T4 (FT4) levels and inappropriately normal levels of thyroid-stimulating hormone (TSH). Five unrelated families reported. Most identified through standard NBS. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.2001 | 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+ v0.1993 | 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+ v0.1989 | IARS |
Zornitza Stark gene: IARS was added gene: IARS was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IARS were set to 27426735; 34194004 Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093 Review for gene: IARS was set to AMBER Added comment: Established gene-disease association. Congenital, multi-system metabolic disorder. N=1 study of Isoleucine supplementation and protein fortification (2.5mg/kg/day, during illness 3.5 g/kg/day) with some clinical improvement. 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+ v0.1979 | NLGN4X | Zornitza Stark Mode of inheritance for gene: NLGN4X was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1978 | NLGN4X | Zornitza Stark reviewed gene: NLGN4X: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked MIM#300495; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1947 | 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+ v0.1943 | 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+ v0.1935 | 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+ v0.1933 | 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+ v0.1932 |
Zornitza Stark Panel name changed from gNBS to Baby Screen+ newborn screening Panel status changed from internal to public |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1883 | 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+ v0.1872 | 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 | HMGCS2 |
Lilian Downie gene: HMGCS2 was added gene: HMGCS2 was added to gNBS. Sources: Expert list Mode of inheritance for gene: HMGCS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMGCS2 were set to PMID: 32259399, 32470406 Phenotypes for gene: HMGCS2 were set to HMG-CoA synthase-2 deficiency MIM#605911 Penetrance for gene: HMGCS2 were set to Incomplete Review for gene: HMGCS2 was set to AMBER Added comment: Metabolic disorder; patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. Recover completely between illnesses, do develop fatty liver. ?incomplete penetrance or variable age of onset On GUARDIAN and Rx Genes Rx IV glucose during acute episodes, avoid prolonged fasting Metabolic parameters are normal in between episodes, so no ability to do a confirmatory biochemical test. Pros: readily treatable if child has an episode Cons: unncessary worry as child may never have episode Super rare ?30 cases Discuss with JC? Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1866 | ACTA2 | Zornitza Stark Mode of inheritance for gene: ACTA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | LAMP2 | Ari Horton reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Childhood onset cardiomyopathy (Severe), Neuordevelopmental phenotype; 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+ v0.1865 | GATA4 | Ari Horton reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, Congenital Heart Disease, Arrhythmia, Extra-cardiac Manifestations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1865 | ACTA2 | Ari Horton reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1860 | 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+ v0.1859 | 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+ v0.1849 | 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+ v0.1845 | CASQ2 |
Zornitza Stark changed review comment from: Well established gene-disease association. ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided. 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. For review.; to: Well established gene-disease association. ClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided. 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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1837 | 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+ v0.1834 | 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+ v0.1825 | PMM2 |
Zornitza Stark changed review comment from: Well established gene-disease association. Two clinical presentations - solely neurologic form and a neurologic-multivisceral form Mortality approximately 20% in first 2 years Treatment: epalrestat PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. For review: uncertain if in use for CDG; to: Well established gene-disease association. Two clinical presentations - solely neurologic form and a neurologic-multivisceral form Mortality approximately 20% in first 2 years Treatment: epalrestat PMID 31636082: Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. Treatment not well established in patients. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1819 | ECHS1 |
Zornitza Stark gene: ECHS1 was added gene: ECHS1 was added to gNBS. Sources: Expert list treatable, metabolic tags were added to gene: ECHS1. Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ECHS1 were set to 32642440 Phenotypes for gene: ECHS1 were set to Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277 Review for gene: ECHS1 was set to GREEN Added comment: Well established gene-disease association. Usually presents in infancy. Treatable-ID – level 4 evidence: valine restriction improves psychomotor/cognitive development/IQ; improves neurological manifestations (incl. neuro-imaging); improves systemic manifestations (PMID: 32642440) Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1815 | DNAJC12 |
Zornitza Stark gene: DNAJC12 was added gene: DNAJC12 was added to gNBS. Sources: Expert Review treatable, metabolic tags were added to gene: DNAJC12. Mode of inheritance for gene: DNAJC12 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAJC12 were set to Hyperphenylalaninemia, mild, non-BH4-deficient, MIM#617384 Review for gene: DNAJC12 was set to GREEN Added comment: Established gene-disease association. Manifests as mild hyperphenylalaninaemia that would be detected on NBS – untreated results in axial hypotonia, dystonia, nystagmus, global developmental delay, and intellectual disability. From Treatable-ID, level 4 evidence that BH4, L-dopa + carbidopa +/-, 5- hydroxytryptophan improves psychomotor/cognitive development/IQ; prevents, halts, or slows clinical deterioration and improves neurological manifestations. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1781 | 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+ v0.1778 | 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+ v0.1772 | 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+ v0.1770 | 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 Phenotypes for gene: BRCA1 were changed from Breast-ovarian cancer, familial, 1 to Fanconi anemia, complementation group S, MIM# 617883 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1766 | BRCA1 | Zornitza Stark reviewed gene: BRCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group S, MIM# 617883; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1766 | BRCA2 | Zornitza Stark Phenotypes for gene: BRCA2 were changed from Fanconi anaemia, complementation group D, MIM#1 605724; Fanconi anemia, complementation group D1; Breast-ovarian cancer, familial, 2 to Fanconi anaemia, complementation group D1, MIM# 605724 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1763 | BRCA2 | Zornitza Stark reviewed gene: BRCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group D1, MIM# 605724; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1755 | DSC2 | Zornitza Stark Mode of inheritance for gene: DSC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1748 | 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+ v0.1746 | MEN1 |
Zornitza Stark changed review comment from: For review re age of onset: surveillance starts age 5, disease onset generally later.; to: For review re age of onset: surveillance starts age 5, disease onset generally later. Rated as 'strong actionability' in paediatric patients by ClinGen. Parathyroid tumors, which cause PHPT, are the most common feature and the first clinical manifestation in 90% of individuals with MEN1 with onset typically between ages 20 and 25 years. Almost all (95-100%) individuals with MEN1 can expect to have PHPT by age 50 years. However, MEN1 affects all age groups, with a reported age range of 5 to 81 years; 17% of MEN1 tumors are diagnosed under age 21. Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by age 50. The cause of death in 50-70% of cases is due to a malignant tumor process or sequelae of the disease, with malignancies accounting for 30% of all deaths. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1736 | 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+ v0.1734 | 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+ v0.1732 | 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+ v0.1730 | 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+ v0.1728 | 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+ v0.1724 | 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+ v0.1722 | 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+ v0.1714 | TAT | Zornitza Stark Tag metabolic tag was added to gene: TAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1714 | STAT3 |
Zornitza Stark Tag treatable tag was added to gene: STAT3. Tag immunological tag was added to gene: STAT3. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1708 | 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+ v0.1701 | GLA | Zornitza Stark edited their review of gene: GLA: Changed rating: AMBER; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1698 | F9 | Zornitza Stark reviewed gene: F9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophilia B (MIM#306900); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1698 | F8 | Zornitza Stark reviewed gene: F8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Haemophilia A, MIM# 306700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1632 | SLC25A13 | John Christodoulou reviewed gene: SLC25A13: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301360, PMID: 31255436; Phenotypes: neonatal cholestatic jaundice, neuropsychiatric abnormalities, ID, failure to thrive, hepatomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1612 | POU3F4 | Zornitza Stark reviewed gene: POU3F4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, X-linked 2, MIM#304400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1612 | PYGL | John Christodoulou edited their review of gene: PYGL: Changed publications: PMID: 30659246, PMID: 35725468, PMID: 20301760; Changed phenotypes: hepatomegaly, hypoglycaemia, cardiomyopathy, short stature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1609 | PORCN | Zornitza Stark Mode of inheritance for gene: PORCN was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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 | 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+ v0.1589 | PQBP1 | Zornitza Stark reviewed gene: PQBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renpenning syndrome, MIM#309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1579 | PLP1 | Zornitza Stark reviewed gene: PLP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1549 | PHF6 | Zornitza Stark edited their review of gene: PHF6: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1547 | PHF6 | Zornitza Stark reviewed gene: PHF6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Borjeson-Forssman-Lehmann syndrome, MIM# 301900; 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+ v0.1546 | PHEX | Zornitza Stark Mode of inheritance for gene: PHEX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.1545 | PHEX | Zornitza Stark reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: None; Publications: 29791829; Phenotypes: Hypophosphatemic rickets, MIM#307800; 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+ v0.1531 | TAZ | Seb Lunke reviewed gene: TAZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Barth syndrome, MIM# 302060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1530 | TIMM8A | Lilian Downie reviewed gene: TIMM8A: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20301395; Phenotypes: Mohr-Tranebjaerg syndrome MIM#304700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1521 | STXBP2 |
Seb Lunke changed review comment from: Established gene-disease association. Childhood onset, multi-system disorder Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity; to: Established gene-disease association. Childhood onset, hyperinflammatory disorder Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1510 | STAT3 | Seb Lunke Marked gene: STAT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1510 | STAT3 | Seb Lunke Gene: stat3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1510 | STAT3 | Seb Lunke Phenotypes for gene: STAT3 were changed from Hyper-IgE recurrent infection syndrome to Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1509 | STAT3 | Seb Lunke reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1487 | SPTA1 | Seb Lunke Mode of inheritance for gene: SPTA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1452 | RFWD3 | Zornitza Stark reviewed gene: RFWD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group W, MIM# 617784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1449 | 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+ v0.1447 | 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 reviewed gene: RFXANK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MHC class II deficiency, complementation group B MIM# 209920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1425 | 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+ v0.1420 | DMD | Zornitza Stark reviewed gene: DMD: Rating: GREEN; Mode of pathogenicity: None; Publications: 36278620, 36152336, 35562557, 35307847; Phenotypes: Duchenne muscular dystrophy MIM#310200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1420 | SLC2A1 | Zornitza Stark reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777, Dystonia 9, MIM#601042, GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1406 | SMPX | Seb Lunke reviewed gene: SMPX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, X-linked 4, MIM# 300066 Myopathy, distal, 7, adult-onset, X-linked, MIM# 301075; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1403 | SMC1A | Seb Lunke Mode of inheritance for gene: SMC1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1401 | SMC1A | Seb Lunke reviewed gene: SMC1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 2, MIM# 300590, Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1381 | RPS6KA3 | Zornitza Stark reviewed gene: RPS6KA3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Lowry syndrome MIM# 303600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1364 | SLX4 | Seb Lunke reviewed gene: SLX4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group P, MIM# 613951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1361 | SLC9A6 | Seb Lunke reviewed gene: SLC9A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1355 | SLC6A8 | Seb Lunke reviewed gene: SLC6A8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral creatine deficiency syndrome 1, MIM# 300352; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1323 | SLC2A1 | Seb Lunke reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777, Dystonia 9, MIM#601042, GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1309 | SLC35A2 | Seb Lunke reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32103184; Phenotypes: Congenital disorder of glycosylation, type IIm, MIM #300896; 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+ v0.1303 | GLA | Zornitza Stark reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fabry disease (MIM# 301500); 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+ v0.1297 | HCFC1 | Zornitza Stark Mode of inheritance for gene: HCFC1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1278 | HSD17B10 | Zornitza Stark reviewed gene: HSD17B10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: HSD10 mitochondrial disease, MIM# 300438; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1275 | HPRT1 | Zornitza Stark reviewed gene: HPRT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lesch-Nyhan syndrome, MIM# 300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1272 | PIGA | John Christodoulou reviewed gene: PIGA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32256299, PMID: 24706016, PMID: 25885527, PMID: 24259184; Phenotypes: hypotonia, infantile epileptic encephalopathy, facial dysmorphism; 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 | 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+ v0.1257 | SLC5A6 |
Seb Lunke gene: SLC5A6 was added gene: SLC5A6 was added to gNBS. Sources: Literature for review tags were added to gene: SLC5A6. Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal Review for gene: SLC5A6 was set to GREEN Added comment: Established gene-disease association. Childhood onset, multisystemic metabolic disorder with highly variable manifestations Treatment: biotin, pantothenic acid, lipoate Non-genetic confirmatory test: no Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1251 | ADA2 |
Seb Lunke gene: ADA2 was added gene: ADA2 was added to gNBS. Sources: Literature for review tags were added to gene: ADA2. Mode of inheritance for gene: ADA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ADA2 were set to Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome, MIM# 615688 Review for gene: ADA2 was set to GREEN Added comment: Established gene-disease association. Childhood onset but variable, multisystem disorder with variable severity. Onset common <5 years Treatment: TNF inhibitor, hematopoietic stem cell transplantation, IL6 receptor antibody (tocilizumab) Non-genetic confirmatory test: plasma ADA2 enzyme activity Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1250 | IL2RG | Zornitza Stark edited their review of gene: IL2RG: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1248 | IKBKG | Zornitza Stark reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 33 (300636); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1247 | IGSF1 | Zornitza Stark reviewed gene: IGSF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypothyroidism, central, and testicular enlargement, MIM# 300888; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1243 | IDS | Zornitza Stark edited their review of gene: IDS: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1201 | HDAC8 | Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.1199 | HDAC8 | Zornitza Stark reviewed gene: HDAC8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 5, MIM# 300882; 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+ v0.1195 | GJB1 | Zornitza Stark Mode of inheritance for gene: GJB1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.1193 | GJB1 | Zornitza Stark reviewed gene: GJB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800; 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+ v0.1154 | HCFC1 | John Christodoulou reviewed gene: HCFC1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 20301503, PMID: 26893841, PMID: 35337626; Phenotypes: nonimmune hydrops, cardiomyopathy, intrauterine growth restriction, microcephaly, global dev delay, ID, seizures; 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+ v0.1148 | 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+ v0.1129 | 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+ v0.1127 | GPR143 | Zornitza Stark reviewed gene: GPR143: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ocular albinism, type I, Nettleship-Falls type, MIM# 300500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1122 | 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 | 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 | GSS | Zornitza Stark Phenotypes for gene: GSS were changed from Glutathione synthetase deficiency to Glutathione synthetase deficiency, MIM# 266130; Haemolytic anemia due to glutathione synthetase deficiency 231900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1119 | GSS | Zornitza Stark reviewed gene: GSS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutathione synthetase deficiency, MIM# 266130, Haemolytic anemia due to glutathione synthetase deficiency 231900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1118 | GCM2 |
Zornitza Stark gene: GCM2 was added gene: GCM2 was added to gNBS. Sources: Expert Review Mode of inheritance for gene: GCM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: GCM2 were set to 27745835; 20190276; 34967908; 35038313 Phenotypes for gene: GCM2 were set to Hyperparathyroidism 4, OMIM #617343; Hypoparathyroidism, familial isolated 2, OMIM #618883 Review for gene: GCM2 was set to GREEN Added comment: Well established association. GoF for AD hyperparathyroidism, and LoF for AR hypoparathyroidism. Variable age of onset. Treatment for hypoPTH: calcium carbonate, calcitriol. HyperPTH: surgery? Non-genetic confirmatory tests: calcium, phosphate, parathyroid hormone Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1093 | KDM6A | Zornitza Stark Mode of inheritance for gene: KDM6A was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.1091 | KDM6A | Zornitza Stark reviewed gene: KDM6A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Kabuki syndrome 2, 300867; 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+ v0.1074 | KRT14 | Zornitza Stark Mode of inheritance for gene: KRT14 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1051 | 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+ v0.1047 | TSHR | Zornitza Stark Phenotypes for gene: TSHR were changed from Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200 to Hypothyroidism, congenital, nongoitrous, 1 - MIM#275200; HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1038 | FANCA | Zornitza Stark Phenotypes for gene: FANCA were changed from Fanconi anaemia, MIM#227650 to Fanconi anaemia, complementation group A, MIM# 227650; MONDO:0009215 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1037 | FANCA | Zornitza Stark reviewed gene: FANCA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group A, MIM# 227650, MONDO:0009215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1037 | FANCB | Zornitza Stark Phenotypes for gene: FANCB were changed from Fanconi anaemia, MIM#300514 to Fanconi anaemia, complementation group B, MIM# 300514 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1036 | FANCB | Zornitza Stark reviewed gene: FANCB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group B, MIM# 300514; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1036 | FANCC | Zornitza Stark Phenotypes for gene: FANCC were changed from Fanconi anaemia, MIM#227645 to Fanconi anemia, complementation group C, MIM# 227645; MONDO:0009213 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1035 | FANCC | Zornitza Stark reviewed gene: FANCC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group C, MIM# 227645 MONDO:0009213; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1035 | FANCD2 | Zornitza Stark Phenotypes for gene: FANCD2 were changed from Fanconi anaemia, MIM#227646 to Fanconi anaemia, complementation group D2, MIM# 227646; MONDO:0009214 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1034 | FANCD2 | Zornitza Stark reviewed gene: FANCD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group D2, MIM# 227646, MONDO:0009214; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1034 | FANCG | Zornitza Stark reviewed gene: FANCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group G, MIM# 614082, MONDO:0013565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1034 | FANCI | Zornitza Stark reviewed gene: FANCI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group I, MIM# 609053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1030 | GDAP1 | Zornitza Stark Mode of inheritance for gene: GDAP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.1023 | FGD1 | Zornitza Stark reviewed gene: FGD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aarskog-Scott syndrome, MIM # 305400, Mental retardation, X-linked syndromic 16, MIM# 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.1002 | FOXA2 | Zornitza Stark Mode of inheritance for gene: FOXA2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.992 | FOXP3 | Zornitza Stark reviewed gene: FOXP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked , MIM#304790; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.910 | EMD | Zornitza Stark reviewed gene: EMD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emery-Dreifuss muscular dystrophy 1, X-linked MIM#310300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.898 | EDARADD | Zornitza Stark Mode of inheritance for gene: EDARADD was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.892 | 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+ v0.890 | 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 | TSHR | Lilian Downie reviewed gene: TSHR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 8981017, PMID: 20515734; Phenotypes: HYPERTHYROIDISM, FAMILIAL GESTATIONAL HYPERTHYROIDISM, NONAUTOIMMUNE HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 1, CHNG1; Mode of inheritance: BOTH monoallelic and 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+ v0.864 | 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 | DGUOK |
Zornitza Stark changed review comment from: Well established gene disease association. Variable age of onset ranging from severe neonatal presentations to adult. See comments below about treatment: emerging approaches. For review.; to: Well established gene disease association. Variable age of onset ranging from severe neonatal presentations to adult. See comments below about treatment: emerging approaches. May not be eligible for liver transplant due to multi-system involvement. For review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.857 | PALB2 | Zornitza Stark reviewed gene: PALB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group N, OMIM 610832; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.856 | DHCR7 |
Zornitza Stark changed review comment from: Well established gene-disease association. Perinatal onset. Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes. For review.; to: Well established gene-disease association. Perinatal onset. Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes but some improvement seen in metabolic parameters, and behavioural manifestations. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.856 | DHCR7 |
Zornitza Stark changed review comment from: Well established gene-disease association. Perinatal onset. Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes. For review.; to: Well established gene-disease association. Perinatal onset. Cholesterol supplementation accepted as standard treatment. Questionable to what extent treatment improves outcomes. Not listed as treatable on rx-genes. For review. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.847 | DCX | Zornitza Stark reviewed gene: DCX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked, MIM# 300067, Subcortical laminal heterotopia, X-linked 300067; 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+ v0.845 | COL4A5 | Zornitza Stark Mode of inheritance for gene: COL4A5 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.844 | COL4A5 | Zornitza Stark reviewed gene: COL4A5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alport syndrome 1, X-linked, MIM# 301050; 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+ v0.825 | UBE2T | Zornitza Stark reviewed gene: UBE2T: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group T MIM#616435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.801 | UBE2T | Lilian Downie reviewed gene: UBE2T: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32646888, PMID: 26119737, PMID: 26046368, PMID: 26085575; Phenotypes: Fanconi anemia, complementation group T MIM#616435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.787 | CYP27A1 |
John Christodoulou changed review comment from: treatable with chenodeoxycholic acid and pravastatin; GeneReviews - www.ncbi.nlm.nih.gov/books/NBK1409/#ctx.Summary Best effect if started early (PMID: 7964884); to: Onset of disease can be in infancy childhood, with a case made for newborn screening/genetic testing because of effective treatments being available - PMID: 33630770 treatable with chenodeoxycholic acid and pravastatin; GeneReviews - www.ncbi.nlm.nih.gov/books/NBK1409/#ctx.Summary Best effect if started early (PMID: 7964884) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.785 | CYBB | Zornitza Stark reviewed gene: CYBB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chronic granulomatous disease, X-linked, MIM# 306400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.735 | PDHA1 | Zornitza Stark Mode of inheritance for gene: PDHA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.734 | PDHA1 | Zornitza Stark reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency, MIM# 312170; 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+ v0.720 | MYO6 | Zornitza Stark Mode of inheritance for gene: MYO6 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.719 | PALB2 | David Amor reviewed gene: PALB2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anemia, complementation group N, OMIM 610832 (AR), Breast cancer, susceptibility to (OMIM 114480) (AD); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.719 | PAK3 | David Amor reviewed gene: PAK3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 300558, Intellectual developmental disorder, X-linked 30; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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 | OTC | John Christodoulou reviewed gene: OTC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hyperammonaemia, encephalopathy, liver 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+ v0.719 | 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 | NPC1 | John Christodoulou reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29625568, PMID: 30732631; Phenotypes: hepatosplenomegaly, cholestatic jaundice, gaze palsy, ID, dystonia, dementia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.715 | SLC16A2 | Seb Lunke reviewed gene: SLC16A2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Allan-Herndon-Dudley syndrome, MIM# 300523; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.695 | SH2D1A | Seb Lunke reviewed gene: SH2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301580; Phenotypes: Lymphoproliferative syndrome, X-linked, 1, MIM# 308240; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.670 | OTC | David Amor reviewed gene: OTC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 311250 Ornithine transcarbamylase deficiency; 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+ v0.664 | 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+ v0.663 | LDLR | Zornitza Stark Mode of inheritance for gene: LDLR was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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+ v0.660 | COQ8B |
Zornitza Stark changed review comment from: Well established gene-disease association. Disease onset typically between ages 10 and 20 years, although several had earlier onset, including 1 patient with onset in the first year of life. Treatment: CoQ10 supplementation, improves nephrotic features For review: re age of onset; to: Well established gene-disease association. Disease onset typically between ages 10 and 20 years, although several had earlier onset, including 1 patient with onset in the first year of life. Treatment: CoQ10 supplementation, improves nephrotic features For review: re age of onset -- predominantly later onset, so not included |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.640 | CLCN5 | Zornitza Stark reviewed gene: CLCN5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dent disease, MIM#300009; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.638 | CHM | Zornitza Stark reviewed gene: CHM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Choroideraemia MIM#303100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.634 | CFP | Zornitza Stark reviewed gene: CFP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Properdin deficiency, X-linked MIM#312060; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.607 | CDKL5 | Zornitza Stark reviewed gene: CDKL5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 2, MIM 300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.602 | CD40LG | Zornitza Stark reviewed gene: CD40LG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency, X-linked, with hyper-IgM MIM# 308230; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.586 | COQ7 |
Zornitza Stark changed review comment from: Four families reported. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations.; to: Four families reported only. Treatment: CoQ10 supplementation can limit disease progression and reverse some clinical manifestations. However this advice applies to the whole group of related conditions, and data on this particular condition in terms of natural history and response to treatment is currently limited. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.585 | BCHE |
Zornitza Stark changed review comment from: Well established gene-disease association. Individuals are asymptomatic unless exposed to triggering agents. Consider as a separate pharmacogenomic offering? For review.; to: Well established gene-disease association. Individuals are asymptomatic unless exposed to triggering agents. Consider as a separate pharmacogenomic offering? Group review: preventative intervention available by placing alerts in medical records. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.575 | CAV3 | Zornitza Stark Phenotypes for gene: CAV3 were changed from Caveolinopathy; Muscular dystrophy, limb-girdle, type IC to Myopathy, distal, Tateyama type MIM#614321; Rippling muscle disease 2 MIM#606072; Creatine phosphokinase, elevated serum MIM#123320 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.573 | CAV3 | Zornitza Stark reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, distal, Tateyama type MIM#614321, Rippling muscle disease 2 MIM#606072, Creatine phosphokinase, elevated serum MIM#123320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.567 | CASK | Zornitza Stark Mode of inheritance for gene: CASK was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.565 | CASK | Zornitza Stark reviewed gene: CASK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; 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+ v0.559 | CACNA1F | Zornitza Stark Phenotypes for gene: CACNA1F were changed from Night blindness, congenital stationary (complete), 1A, X-linked to Aland Island eye disease MIM#300600; Cone-rod dystrophy, X-linked, 3 MIM#300476; Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.557 | CACNA1F | Zornitza Stark reviewed gene: CACNA1F: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Aland Island eye disease MIM#300600, Cone-rod dystrophy, X-linked, 3 MIM#300476, Night blindness, congenital stationary (incomplete), 2A, X-linked MIM#300071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.503 | WAS | Lilian Downie reviewed gene: WAS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301357; Phenotypes: Wiskott-Aldrich syndrome MIM#301000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.503 | XIAP | Lilian Downie reviewed gene: XIAP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:22228567, 20489057, 17080092, 24942515, 25943627; Phenotypes: Lymphoproliferative syndrome, X-linked, 2 MIM#300635; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.490 | G6PD | Alison Yeung reviewed gene: G6PD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemolytic anemia, G6PD deficient (favism), MIM# 300908; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.490 | BRIP1 | Zornitza Stark reviewed gene: BRIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fanconi anaemia, complementation group J, MIM# 609054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.476 | OPA1 | Zornitza Stark Mode of inheritance for gene: OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.474 | OPA1 | Zornitza Stark reviewed gene: OPA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)MIM# 616896, Behr syndrome MIM#210000, AR, Optic atrophy 1, MIM#165500, Optic atrophy plus syndrome, MIM# 125250; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.472 | OFD1 | Zornitza Stark reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 23, MIM# 300424, Joubert syndrome 10, MIM# 300804, Orofaciodigital syndrome I, MIM# 311200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.470 | OCRL | Zornitza Stark reviewed gene: OCRL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Dent disease 2, MIM# 300555, Lowe syndrome , MIM#309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.460 | NR0B1 | Zornitza Stark reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hypoplasia, congenital (MIM# 300200); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.438 | OFD1 | David Amor reviewed gene: OFD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Orofaciodigital syndrome I; 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+ v0.425 | OCRL | David Amor reviewed gene: OCRL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lowe syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.419 | NDP | Zornitza Stark reviewed gene: NDP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease, MIM# 310600; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.410 | MYO6 | Zornitza Stark Mode of inheritance for gene: MYO6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.409 | MYO6 | Zornitza Stark reviewed gene: MYO6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 22, MIM# 606346, Deafness, autosomal recessive 37, MIM# 607821; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.380 | MTR | Zornitza Stark Phenotypes for gene: MTR were changed from Methylmalonic aciduria and homocystinuria, MIM#250940 to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.378 | MTR | Zornitza Stark reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.376 | MTM1 | Zornitza Stark reviewed gene: MTM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.337 | LAMB3 | Zornitza Stark Mode of inheritance for gene: LAMB3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.315 | MED12 | Zornitza Stark reviewed gene: MED12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ohdo syndrome, X-linked MIM#300895, Lujan-Fryns syndrome MIM#309520, Opitz-Kaveggia syndrome MIM#305450, Hardikar syndrome, MIM# 301068; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.314 | MECP2 | Zornitza Stark Mode of inheritance for gene: MECP2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.312 | MECP2 | Zornitza Stark reviewed gene: MECP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: MECP2-related disorders Rett syndrome, MIM# 312750 Mental retardation, X-linked, syndromic 13, MIM# 300055; 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+ v0.292 | SLC5A2 | Zornitza Stark Mode of inheritance for gene: SLC5A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.290 | SLC5A2 | Zornitza Stark reviewed gene: SLC5A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Renal glucosuria, MIM# 233100; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.288 | BTK | Zornitza Stark reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Agammaglobulinaemia, X-linked 1, MIM# 300755; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.276 | TAT | Zornitza Stark Marked gene: TAT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.276 | TAT | Zornitza Stark Gene: tat has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.276 | TAT | Zornitza Stark Tag treatable tag was added to gene: TAT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.276 | TAT | Zornitza Stark reviewed gene: TAT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tyrosinaemia, type II, MIM# 276600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | ETFA |
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, D,L-3-hydroxybutyrate 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, D,L-3-hydroxybutyrate (PMID 31904027) Non-genetic confirmatory tests: plasma acylcarnitine profile, urine organic acid analysis |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | NR0B1 | David Amor reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital adrenal hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | NDP | David Amor reviewed gene: NDP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Norrie disease; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | MYO6 | David Amor reviewed gene: MYO6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 22, Deafness, autosomal recessive 37; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | MYBPC1 | David Amor reviewed gene: MYBPC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lethal congenital contracture syndrome 4 (AR), Arthrogryposis, distal, type 1B; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | MTR | David Amor reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25526710; Phenotypes: Homocystinuria-megaloblastic anemia, cblG complementation type; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | MTM1 | David Amor reviewed gene: MTM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | MPZ | David Amor reviewed gene: MPZ: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: CMT1B (AD), Dejerine-Sottas disease (AR); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.274 | ZIC3 | Lilian Downie reviewed gene: ZIC3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29442328, PMID: 27406248; Phenotypes: X linked heterotaxy and congenital heart defects MIM:306955; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.271 | HADHA |
Zornitza Stark changed review comment from: Well established gene-disease association. Clinical presentation is characterised by early-onset cardiomyopathy, hypoglycaemia, neuropathy, and pigmentary retinopathy, and sudden death Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin; to: Well established gene-disease association. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy. Treatment: IV glucose during acute episodes, avoid fasting, carnitine, restrict LCFA, bezafibrate, triheptanoin |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.270 | MFN2 | David Amor reviewed gene: MFN2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth Neuropathy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.270 | MED12 | David Amor reviewed gene: MED12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: FG syndrome, intellectual disability, Lujan syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.270 | MECP2 | David Amor reviewed gene: MECP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Rett syndrome; 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+ v0.270 | BTD |
Zornitza Stark changed review comment from: Well established gene-disease association. Variable severity and age of presentation, predominantly with cutaneous and neurologic abnormalities Treatment: biotin Non-genetic confirmatory testing: biotinidase enzyme activity in serum or plasma; to: Well established gene-disease association. Variable severity and age of presentation, predominantly with cutaneous and neurologic abnormalities. Phenotype can be difficult to predict from genotype, however note currently included in tNBS. Treatment: biotin Non-genetic confirmatory testing: biotinidase enzyme activity in serum or plasma |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.266 | BTK | John Christodoulou reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.241 | MCFD2 |
David Amor changed review comment from: Gene-disease association: strong but rare. Onset: birth Treatment: clotting factor supplementation, However only reported to cause mild-moderate bleeding tendency so consider excluding?; to: Gene-disease association: strong but rare. Onset: birth Treatment: clotting factor supplementation, However only reported to cause mild-moderate bleeding tendency so consider excluding? |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.229 | MBTPS2 | David Amor reviewed gene: MBTPS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: IFAP syndrome: ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); 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+ v0.222 | 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. 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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.219 | LDLR | Zornitza Stark Mode of inheritance for gene: LDLR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.218 | LDLR | Zornitza Stark edited their review of gene: LDLR: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.213 | LAMP2 | Zornitza Stark Mode of inheritance for gene: LAMP2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to 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+ v0.211 | LAMP2 | Zornitza Stark reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Danon disease, MIM# 300257; 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+ v0.209 | LAMB3 | Zornitza Stark reviewed gene: LAMB3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amelogenesis imperfecta, type IA, MIM# 104530, Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.205 | L1CAM | Zornitza Stark reviewed gene: L1CAM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus due to aqueductal stenosis, MIM# 307000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.199 | LDLR | David Amor reviewed gene: LDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: familial hypercholesterolemia; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.199 | LAMP2 | David Amor reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Danon disease - cardiomyopathy, retinal disease, cognitive dysfunction; 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+ v0.199 | L1CAM | David Amor reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked hydrocephalus, MASA syndrome, X-linked corpus callosum agenesis; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.199 | L1CAM | David Amor reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: X-linked hydrocephalus, MASA syndrome, X-linked corpus callosu agenesis; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.199 | TAT | John Christodoulou reviewed gene: TAT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.160 | ATP7A | Zornitza Stark edited their review of gene: ATP7A: Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.158 | ATRX | Zornitza Stark reviewed gene: ATRX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alpha-thalassemia/mental retardation syndrome, MIM# 301040, Intellectual disability-hypotonic facies syndrome, X-linked, MIM# 309580; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.126 | ARX | Zornitza Stark reviewed gene: ARX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly, X-linked 2, MIM# 300215; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.119 | AR | Zornitza Stark reviewed gene: AR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.117 | AVPR2 | Zornitza Stark reviewed gene: AVPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes insipidus, nephrogenic, 1 304800; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.79 | AMELX | Zornitza Stark reviewed gene: AMELX: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amelogenesis imperfecta, type 1E, MIM# 301200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.56 | ABCD1 | Zornitza Stark reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenoleukodystrophy, MIM# 300100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.26 | ALAS2 | Zornitza Stark reviewed gene: ALAS2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Anaemia, sideroblastic, 1, MIM# 300751, Protoporphyria, erythropoietic, X-linked, MIM# 300752; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.23 | AIFM1 | Zornitza Stark reviewed gene: AIFM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 6, 300816, Cowchock syndrome, 310490, Deafness, X-linked 5, 300614, Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy, 300232; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ZNF674 |
Zornitza Stark gene: ZNF674 was added gene: ZNF674 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ZNF674 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ZNF674 were set to Mental retardation |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | UBA1 |
Zornitza Stark gene: UBA1 was added gene: UBA1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: UBA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: UBA1 were set to Spinal muscular atrophy, X-linked infantile |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLC6A2 |
Zornitza Stark gene: SLC6A2 was added gene: SLC6A2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: SLC6A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SLC6A2 were set to Orthostatic intolerance |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLC35A2 |
Zornitza Stark gene: SLC35A2 was added gene: SLC35A2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: SLC35A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC35A2 were set to Early-onset epileptic encephalopathy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PRPS1 |
Zornitza Stark gene: PRPS1 was added gene: PRPS1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: PRPS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PRPS1 were set to Charcot-Marie-Tooth disease; Arts syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PHKA1 |
Zornitza Stark gene: PHKA1 was added gene: PHKA1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: PHKA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PHKA1 were set to Phosphorylase kinase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | NSDHL |
Zornitza Stark gene: NSDHL was added gene: NSDHL was added to gNBS. Sources: Expert Review Red,BabySeq Category A gene,BabySeq Category C gene Mode of inheritance for gene: NSDHL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NSDHL were set to CK syndrome; CHILD syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | NAA10 |
Zornitza Stark gene: NAA10 was added gene: NAA10 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NAA10 were set to N-terminal acetyltransferase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | IGBP1 |
Zornitza Stark gene: IGBP1 was added gene: IGBP1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: IGBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IGBP1 were set to Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | HCCS |
Zornitza Stark gene: HCCS was added gene: HCCS was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: HCCS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: HCCS were set to Microphthalmia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GPX1 |
Zornitza Stark gene: GPX1 was added gene: GPX1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: GPX1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GPX1 were set to Hemolytic anemia due to glutathione peroxidase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GPC4 |
Zornitza Stark gene: GPC4 was added gene: GPC4 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: GPC4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GPC4 were set to Simpson-Golabi-Behmel syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FHL1 |
Zornitza Stark gene: FHL1 was added gene: FHL1 was added to gNBS. Sources: Expert Review Red,BabySeq Category A gene,BabySeq Category C gene Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FHL1 were set to Myofibrillar myopathy; Emery-Dreifuss muscular dystrophy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FAAH2 |
Zornitza Stark gene: FAAH2 was added gene: FAAH2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: FAAH2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FAAH2 were set to Autism spectrum disorder |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | BRCA2 |
Zornitza Stark Source Expert Review Red was added to BRCA2. Source BabySeq Category A gene was added to BRCA2. Source BabySeq Category C gene was added to BRCA2. Mode of inheritance for gene BRCA2 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Added phenotypes Fanconi anemia, complementation group D1; Breast-ovarian cancer, familial, 2 for gene: BRCA2 Rating Changed from Green List (high evidence) to Red List (low evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | B3GAT3 |
Zornitza Stark gene: B3GAT3 was added gene: B3GAT3 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: B3GAT3 were set to Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ATP6AP2 |
Zornitza Stark gene: ATP6AP2 was added gene: ATP6AP2 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATP6AP2 were set to X-linked recessive intellectual deficit - epilepsy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ATN1 |
Zornitza Stark gene: ATN1 was added gene: ATN1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ATN1 were set to Dentatorubral-pallidoluysian atrophy 1 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ARSE |
Zornitza Stark gene: ARSE was added gene: ARSE was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ARSE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ARSE were set to Chondrodysplasia punctata, X-linked recessive |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ARHGEF9 |
Zornitza Stark gene: ARHGEF9 was added gene: ARHGEF9 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ARHGEF9 were set to Hyperekplexia and epilepsy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | AGPS |
Zornitza Stark gene: AGPS was added gene: AGPS was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: AGPS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AGPS were set to Rhizomelic chondrodysplasia punctata, type 3 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ABCB7 |
Zornitza Stark gene: ABCB7 was added gene: ABCB7 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ABCB7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ABCB7 were set to Sideroblastic anaemia and ataxia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ZIC3 |
Zornitza Stark gene: ZIC3 was added gene: ZIC3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ZIC3 were set to Heterotaxy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | XIAP |
Zornitza Stark gene: XIAP was added gene: XIAP was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: XIAP were set to Lymphoproliferative syndrome, X-linked, 2, MIM# 300635 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | WAS |
Zornitza Stark gene: WAS was added gene: WAS was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: WAS were set to Neutropenia, severe congenital, X-linked , MIM#300299; Thrombocytopaenia, X-linked, MIM# 313900; Wiskott-Aldrich syndrome, MIM# 301000 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | UBE2T |
Zornitza Stark gene: UBE2T was added gene: UBE2T was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UBE2T were set to Fanconi anaemia, complementation group T, MIM# 616435 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | TSR2 |
Zornitza Stark gene: TSR2 was added gene: TSR2 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: TSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TSR2 were set to Diamond-Blackfan anaemia 14 with mandibulofacial dysostosis, MIM# 300946 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | TRAPPC2 |
Zornitza Stark gene: TRAPPC2 was added gene: TRAPPC2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TRAPPC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TRAPPC2 were set to Spondyloepiphyseal dysplasia tarda |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | TIMM8A |
Zornitza Stark gene: TIMM8A was added gene: TIMM8A was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TIMM8A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TIMM8A were set to Mohr-Tranebjaerg syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | TAZ |
Zornitza Stark gene: TAZ was added gene: TAZ was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: TAZ were set to Barth syndrome, MIM#302060 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | TAT |
Zornitza Stark gene: TAT was added gene: TAT was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TAT were set to Tyrosinemia, type II, MIM#276600 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | STS |
Zornitza Stark gene: STS was added gene: STS was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: STS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: STS were set to Ichthyosis, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | STAT3 |
Zornitza Stark gene: STAT3 was added gene: STAT3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: STAT3 were set to Hyper-IgE recurrent infection syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SMPX |
Zornitza Stark gene: SMPX was added gene: SMPX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: SMPX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SMPX were set to Deafness, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLX4 |
Zornitza Stark gene: SLX4 was added gene: SLX4 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: SLX4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLX4 were set to Fanconi anaemia, complementation group P, MIM# 613951 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLC9A6 |
Zornitza Stark gene: SLC9A6 was added gene: SLC9A6 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC9A6 were set to Christianson syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLC6A8 |
Zornitza Stark gene: SLC6A8 was added gene: SLC6A8 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: SLC6A8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC6A8 were set to Creatine deficiency syndrome, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SLC16A2 |
Zornitza Stark gene: SLC16A2 was added gene: SLC16A2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | SH2D1A |
Zornitza Stark gene: SH2D1A was added gene: SH2D1A was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: SH2D1A were set to Lymphoproliferative syndrome, MIM#308240 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | RS1 |
Zornitza Stark gene: RS1 was added gene: RS1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: RS1 were set to Retinoschisis, X linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | RPS6KA3 |
Zornitza Stark gene: RPS6KA3 was added gene: RPS6KA3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RPS6KA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: RPS6KA3 were set to Coffin-Lowry syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | RPGR |
Zornitza Stark gene: RPGR was added gene: RPGR was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RPGR was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: RPGR were set to Retinitis pigmentosa |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | RFXANK |
Zornitza Stark gene: RFXANK was added gene: RFXANK was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: RFXANK was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RFXANK were set to MHC class II deficiency, complementation group B , MIM#209920 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | RFWD3 |
Zornitza Stark gene: RFWD3 was added gene: RFWD3 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: RFWD3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RFWD3 were set to Fanconi anaemia, complementation group W, MIM# 617784 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PQBP1 |
Zornitza Stark gene: PQBP1 was added gene: PQBP1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PQBP1 were set to Mental retardation |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | POU3F4 |
Zornitza Stark gene: POU3F4 was added gene: POU3F4 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: POU3F4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: POU3F4 were set to Deafness, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PORCN |
Zornitza Stark gene: PORCN was added gene: PORCN was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PORCN was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PORCN were set to Focal dermal hypoplasia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PLP1 |
Zornitza Stark gene: PLP1 was added gene: PLP1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease; Spastic paraplegia 2, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PIGA |
Zornitza Stark gene: PIGA was added gene: PIGA was added to gNBS. Sources: Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PIGA were set to 32694024; 24706016; 26545172; 24357517; 33333793; 22305531 Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PHKA2 |
Zornitza Stark gene: PHKA2 was added gene: PHKA2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PHKA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PHKA2 were set to Phosphorylase kinase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PHEX |
Zornitza Stark gene: PHEX was added gene: PHEX was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: PHEX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant, MIM# 307800 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PHF6 |
Zornitza Stark gene: PHF6 was added gene: PHF6 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PEX7 |
Zornitza Stark gene: PEX7 was added gene: PEX7 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PEX7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PEX7 were set to Rhizomelic chondrodysplasia punctata; Refsum disease |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PDHA1 |
Zornitza Stark gene: PDHA1 was added gene: PDHA1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PALB2 |
Zornitza Stark gene: PALB2 was added gene: PALB2 was added to gNBS. Sources: Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PALB2 were set to 17200671 Phenotypes for gene: PALB2 were set to Fanconi anemia, complementation group N, MIM# 610832 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | PAK3 |
Zornitza Stark gene: PAK3 was added gene: PAK3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PAK3 were set to Mental retardation syndrome, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | OTC |
Zornitza Stark gene: OTC was added gene: OTC was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: OTC was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: OTC were set to Ornithine transcarbamylase deficiency, MIM#311250 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | OFD1 |
Zornitza Stark gene: OFD1 was added gene: OFD1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: OFD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: OFD1 were set to Oral-facial-digital syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | OCRL |
Zornitza Stark gene: OCRL was added gene: OCRL was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: OCRL were set to Lowe oculocerebrorenal syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | NR0B1 |
Zornitza Stark gene: NR0B1 was added gene: NR0B1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: NR0B1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NR0B1 were set to Congenital adrenal hypoplasia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | NDP |
Zornitza Stark gene: NDP was added gene: NDP was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: NDP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: NDP were set to Norrie disease |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MTM1 |
Zornitza Stark gene: MTM1 was added gene: MTM1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MTM1 were set to Myotubular myopathy, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MMAB |
Zornitza Stark gene: MMAB was added gene: MMAB was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MMAB were set to Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type, MIM#251110 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MED12 |
Zornitza Stark gene: MED12 was added gene: MED12 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MED12 were set to Intellectual disability |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MECP2 |
Zornitza Stark gene: MECP2 was added gene: MECP2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MECP2 were set to Rett syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MBTPS2 |
Zornitza Stark gene: MBTPS2 was added gene: MBTPS2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MBTPS2 were set to Ichthyosis follicularis, alopecia & photophobia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | MAD2L2 |
Zornitza Stark gene: MAD2L2 was added gene: MAD2L2 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: MAD2L2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MAD2L2 were set to Fanconi anemia, complementation group V, MIM# 617243 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | LAMP2 |
Zornitza Stark gene: LAMP2 was added gene: LAMP2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: LAMP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: LAMP2 were set to Danon disease |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | L1CAM |
Zornitza Stark gene: L1CAM was added gene: L1CAM was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: L1CAM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: L1CAM were set to X-linked hydrocephalus syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | KDM6A |
Zornitza Stark gene: KDM6A was added gene: KDM6A was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: KDM6A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: KDM6A were set to Kabuki syndrome 2 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | IL2RG |
Zornitza Stark gene: IL2RG was added gene: IL2RG was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: IL2RG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IL2RG were set to Severe combined immunodeficiency, X-linked, MIM#312863 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | IKBKG |
Zornitza Stark gene: IKBKG was added gene: IKBKG was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: IKBKG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IKBKG were set to Incontinentia pigmenti 1 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | IGSF1 |
Zornitza Stark gene: IGSF1 was added gene: IGSF1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: IGSF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IGSF1 were set to Central hypothyroidism and testicular enlargement |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | IDS |
Zornitza Stark gene: IDS was added gene: IDS was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: IDS were set to Mucopolysaccharidosis II |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | HSD17B10 |
Zornitza Stark gene: HSD17B10 was added gene: HSD17B10 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: HSD17B10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: HSD17B10 were set to 17-beta-hydroxysteroid dehydrogenase X deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | HPRT1 |
Zornitza Stark gene: HPRT1 was added gene: HPRT1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: HPRT1 were set to Lesch-Nyhan syndrome 1 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | HDAC8 |
Zornitza Stark gene: HDAC8 was added gene: HDAC8 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: HDAC8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: HDAC8 were set to Cornelia de Lange syndrome-like features, ocular hypertelorism & large fontanelle |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GSS |
Zornitza Stark gene: GSS was added gene: GSS was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: GSS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GSS were set to Glutathione synthetase deficiency |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GPR143 |
Zornitza Stark gene: GPR143 was added gene: GPR143 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: GPR143 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GPR143 were set to Ocular albinism, type I |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GPC3 |
Zornitza Stark gene: GPC3 was added gene: GPC3 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GLA |
Zornitza Stark gene: GLA was added gene: GLA was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GLA were set to Fabry disease |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GJB1 |
Zornitza Stark gene: GJB1 was added gene: GJB1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: GJB1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GJB1 were set to Charcot-Marie-Tooth neuropathy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | GATA1 |
Zornitza Stark gene: GATA1 was added gene: GATA1 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: GATA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GATA1 were set to Blackfan-Diamond anaemia, ORPHA:124; Anaemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835; Congenital erythropoietic porphyria, ORPHA:79277; Thrombocytopenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | G6PD |
Zornitza Stark gene: G6PD was added gene: G6PD was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: G6PD were set to Glucose-6-phosphate dehydrogenase deficiency, MIM#300908 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FOXP3 |
Zornitza Stark gene: FOXP3 was added gene: FOXP3 was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FOXP3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FOXP3 were set to IPEX syndrome, MIM#304790 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FLNA |
Zornitza Stark gene: FLNA was added gene: FLNA was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FLNA were set to Otopalatodigital spectrum disorder |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FGD1 |
Zornitza Stark gene: FGD1 was added gene: FGD1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FANCB |
Zornitza Stark gene: FANCB was added gene: FANCB was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FANCB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FANCB were set to Fanconi anaemia, MIM#300514 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | FAM58A |
Zornitza Stark gene: FAM58A was added gene: FAM58A was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: FAM58A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: FAM58A were set to Syndactyly - telecanthus - anogenital and renal malformations |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | F9 |
Zornitza Stark gene: F9 was added gene: F9 was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: F9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: F9 were set to Haemophilia B, MIM#306900 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | F8 |
Zornitza Stark gene: F8 was added gene: F8 was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: F8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: F8 were set to Haemophilia A, MIM#306700 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ERCC4 |
Zornitza Stark gene: ERCC4 was added gene: ERCC4 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ERCC4 were set to Xeroderma pigmentosum, group F, MIM# 278760; Fanconi anaemia, complementation group Q, MIM# 615272 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | EMD |
Zornitza Stark gene: EMD was added gene: EMD was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: EMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: EMD were set to Muscular dystrophy, Emery-Dreifuss |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | EDA |
Zornitza Stark gene: EDA was added gene: EDA was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: EDA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: EDA were set to Ectodermal dysplasia, hypohidrotic |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | DMD |
Zornitza Stark gene: DMD was added gene: DMD was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: DMD was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: DMD were set to Duchenne muscular dystrophy, MIM# 310200 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | DKC1 |
Zornitza Stark gene: DKC1 was added gene: DKC1 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: DKC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: DKC1 were set to Dyskeratosis congenita, X-linked, MIM# 305000 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | DCX |
Zornitza Stark gene: DCX was added gene: DCX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: DCX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: DCX were set to Lissencephaly, X-linked, MIM# 300067 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CYBB |
Zornitza Stark gene: CYBB was added gene: CYBB was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CYBB was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CYBB were set to Chronic granulomatous disease, MIM#306400 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | COL4A5 |
Zornitza Stark gene: COL4A5 was added gene: COL4A5 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: COL4A5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: COL4A5 were set to Alport syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CLCN5 |
Zornitza Stark gene: CLCN5 was added gene: CLCN5 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CLCN5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CLCN5 were set to Dent disease |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CHM |
Zornitza Stark gene: CHM was added gene: CHM was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CHM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CHM were set to Choroideremia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CFP |
Zornitza Stark gene: CFP was added gene: CFP was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CFP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CFP were set to Properdin deficiency, X-linked, MIM#312060 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CDKL5 |
Zornitza Stark gene: CDKL5 was added gene: CDKL5 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CDKL5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CDKL5 were set to Epileptic encephalopathy, early infantile, 2 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CD40LG |
Zornitza Stark gene: CD40LG was added gene: CD40LG was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CD40LG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CASK |
Zornitza Stark gene: CASK was added gene: CASK was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CASK were set to Mental retardation and microcephaly with pontine and cerebellar hypoplasia |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | CACNA1F |
Zornitza Stark gene: CACNA1F was added gene: CACNA1F was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: CACNA1F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: CACNA1F were set to Night blindness, congenital stationary (complete), 1A, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | BTK |
Zornitza Stark gene: BTK was added gene: BTK was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: BTK was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: BTK were set to Agammaglobulinemia, X-linked 1, MIM#300755 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | BRIP1 |
Zornitza Stark gene: BRIP1 was added gene: BRIP1 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: BRIP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BRIP1 were set to Fanconi anaemia, complementation group J, MIM# 609054 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | BRCA2 |
Zornitza Stark gene: BRCA2 was added gene: BRCA2 was added to gNBS. Sources: BeginNGS,Expert Review Green Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BRCA2 were set to Fanconi anaemia, complementation group D, MIM#1 605724 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | AVPR2 |
Zornitza Stark gene: AVPR2 was added gene: AVPR2 was added to gNBS. Sources: BeginNGS,BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: AVPR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AVPR2 were set to Diabetes insipidus, nephrogenic, MIM#304800 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ATRX |
Zornitza Stark gene: ATRX was added gene: ATRX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ATP7A |
Zornitza Stark gene: ATP7A was added gene: ATP7A was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATP7A were set to Menkes disease, MIM# 309400 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ARX |
Zornitza Stark gene: ARX was added gene: ARX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ARX were set to Lissencephaly, X-linked 2 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | AR |
Zornitza Stark gene: AR was added gene: AR was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green,BabySeq Category C gene Mode of inheritance for gene: AR was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AR were set to Androgen insensitivity, MIM# 300068 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | AMELX |
Zornitza Stark gene: AMELX was added gene: AMELX was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: AMELX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AMELX were set to Amelogenesis imperfecta |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ALAS2 |
Zornitza Stark gene: ALAS2 was added gene: ALAS2 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ALAS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ALAS2 were set to Anemia, sideroblastic, X-linked |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | AIFM1 |
Zornitza Stark gene: AIFM1 was added gene: AIFM1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AIFM1 were set to Cowchock syndrome |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ABCD1 |
Zornitza Stark gene: ABCD1 was added gene: ABCD1 was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ABCD1 were set to Adrenoleukodystrophy |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||