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Mendeliome v1.2557 | SIRT1 | Zornitza Stark Phenotypes for gene: SIRT1 were changed from autoimmune disease, MONDO:0007179 to autoimmune disease, MONDO:0007179; monogenic diabetes MONDO:0015967 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2556 | SIRT1 | Zornitza Stark reviewed gene: SIRT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2479 | SIRT1 | Sangavi Sivagnanasundram reviewed gene: SIRT1: Rating: RED; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008794; Phenotypes: monogenic diabetes MONDO:0015967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2470 | FGB | Bryony Thompson reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24560896; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2470 | FGA | Bryony Thompson reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 10602365, 11460510; Phenotypes: Congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2413 | C19orf44 |
Sangavi Sivagnanasundram gene: C19orf44 was added gene: C19orf44 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: C19orf44 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C19orf44 were set to 40079362 Phenotypes for gene: C19orf44 were set to Late onset retinal dystrophy; MONDO:0019118 Review for gene: C19orf44 was set to GREEN Added comment: 5 biallelic LoF variants were identified in 11 unrelated families of Jewish or Israeli ancestry. All affected individuals present with a form of retinal disorder including perifoveal chorioretinal atrophy and electroretinographic features of rod-cone degeneration. All 5 variants were present in gnomAD v4.1 with varying AF (p.Ser325PhefsTer16 being the most common). Sources: Literature |
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Mendeliome v1.2375 | DUOX2 | Bryony Thompson Added comment: Comment on mode of inheritance: Biallelic evidence for IBD is strong, but the evidence for the monoallelic association is limited. Semidominant inheritance for thyroid dyshormonogenesis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.2285 | MRAP2 |
Zornitza Stark gene: MRAP2 was added gene: MRAP2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MRAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MRAP2 were set to 23869016; 31700171; 27474872; 26795956 Phenotypes for gene: MRAP2 were set to Susceptibility to obesity, MIM#615457 Review for gene: MRAP2 was set to AMBER Added comment: Multiple studies supporting association between rare variants and obesity; however ?monogenic vs susceptibility alleles. Sources: Literature |
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Mendeliome v1.2268 | MGA |
Zornitza Stark gene: MGA was added gene: MGA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MGA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MGA were set to 39600096; 20044811; 39545409 Phenotypes for gene: MGA were set to Syndromic disease, MONDO:0002254, MGA-related; Premature ovarian failure 26, MIM# 621065 Review for gene: MGA was set to AMBER Added comment: Association with syndromic disease: Three individuals with de novo LoF variants reported in individuals with ID and congenital anomalies. Zebrafish model supports role of this transcription factor in organogenesis. Note there are previous, less clear reports of association with NDD/CHD. Gene is constrained for LoF variants in gnomad v4; however, note there are ~30 individuals with LoF variants present. Borderline Green/Amber. Association with POF: LoF variants enriched in a large POF cohort. Familial testing in a small number of families performed. Mouse model supportive. Also borderline Amber/Green. Amber rating until phenotypes and mechanisms of disease for these two associations clarified. Sources: Literature |
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Mendeliome v1.2228 | P2RY8 |
Zornitza Stark gene: P2RY8 was added gene: P2RY8 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: P2RY8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: P2RY8 were set to 34889940 Phenotypes for gene: P2RY8 were set to Systemic lupus erythematosus, MONDO:0007915, P2RY8-related Review for gene: P2RY8 was set to AMBER Added comment: One de novo variant, p.Leu257Phe, absent from gnomAD v4 identified in an individual with early-onset SLE. Subsequent search for additional individuals in large cohorts identified: p. Asn97Lys, inherited from mother, present in 19 individuals in gnomADv4. p.Glu323Gly identified in 6 Chinese individuals, inheritance not determined, present in 51 individuals in gnomADv4. Functional data support the role of the gene in immune tolerance. Role in contributing to the development of SLE is plausible, though not necessarily under a monogenic model. Sources: Literature |
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Mendeliome v1.2133 | IGKC |
Bryony Thompson gene: IGKC was added gene: IGKC was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IGKC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IGKC were set to https://search.clinicalgenome.org/CCID:005121 Phenotypes for gene: IGKC were set to recurrent infections associated with rare immunoglobulin isotypes deficiency MONDO:0013576 Review for gene: IGKC was set to AMBER Added comment: Antibody Deficiencies GCEP classify gene-disease association as Limited (18/05/2021) - at least 6 probands https://search.clinicalgenome.org/CCID:005121 Sources: Expert list |
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Mendeliome v1.2034 | IL7R | Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers. to severe combined immunodeficiency 104 MIM#608971 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.1565 | KLF11 |
Bryony Thompson Added comment: Comment on list classification: Association with monogenic diabetes now Refuted Classification - 02/08/2023. ClinGen Monogenic Diabetes GCEP - https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b1e38a49-7c12-4514-a2a1-109e04da146f-2023-02-08T170000.000Z?page=1&size=25&search= |
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Mendeliome v1.1511 | CCDC88C | Rylee Peters reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.1319 | PTPN4 |
Bryony Thompson changed review comment from: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature; to: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines PMID: 34527963 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature |
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Mendeliome v1.1155 | COL4A3BP |
Ee Ming Wong changed review comment from: - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo. - Several variants transfected into HeLa cells demonstrated gain of CERT activity - CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT; to: - current HGNC symbol: CERT1 - Thirty-one unrelated individuals with twenty-two distinct missense variants. The majority of variants were de novo. - Several variants transfected into HeLa cells demonstrated gain of CERT activity - CERT gain of function in Drosophila melanogaster led to head and brain size defects and impaired locomotor activity, which was corrected by pharmacological inhibition of CERT |
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Mendeliome v1.1052 | TEP1 |
Zornitza Stark gene: TEP1 was added gene: TEP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TEP1 were set to 34543729 Phenotypes for gene: TEP1 were set to Cerebral palsy, MONDO:0006497, TEP1-related Review for gene: TEP1 was set to AMBER Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models. Uncertain if these are risk alleles vs indicative of a monogenic disorder. Note LoF variants in gnomad. As this was a cohort study, inheritance of these variants is unknown. Sources: Literature |
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Mendeliome v1.1033 | MAP3K14 | Zornitza Stark Phenotypes for gene: MAP3K14 were changed from NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels to Immunodeficiency 112, MIM# 620449; NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.1032 | MAP3K14 | Zornitza Stark edited their review of gene: MAP3K14: Changed phenotypes: Immunodeficiency 112, MIM# 620449, NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.477 | CLEC3B |
Chirag Patel gene: CLEC3B was added gene: CLEC3B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CLEC3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLEC3B were set to PMID: 35331648 Phenotypes for gene: CLEC3B were set to Macular dystrophy, retinal, 4, OMIM #619977 Review for gene: CLEC3B was set to GREEN Added comment: 12 affected individuals from 5 multigenerational Japanese families in a small village in Miyazaki diagnosed with autosomal dominant maculoretinopathy. WES identified a pathogenic variant (p.Ala180Asp) in CLEC3B, which encodes tetranectin, a plasminogen kringle-4 binding protein. Variant cosegregated with the ocular phenotype. Mice that received subretinal injections with CLEC3B variant displayed multiple subretinal hyperreflective deposits, reduced retinal thickness, and decreased electroretinographic responses. The optokinetic tracking response indicated that spatial frequency was significantly lower (P < .05), implying impaired visual function in the mice. Sources: Literature |
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Mendeliome v1.385 | VPS33A |
Bryony Thompson changed review comment from: PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts; to: Now two missense variants reported with disease in at least 15 probands/families PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts |
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Mendeliome v1.323 | NODAL |
Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad. The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED. A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance. Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987 |
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Mendeliome v1.202 | DUOX2 | Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis 6 - MIM#607200 to Thyroid dyshormonogenesis 6 - MIM#607200; Inflammatory bowel disease, MONDO:0005265, DUOX2-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v1.110 | POU2AF1 |
Zornitza Stark gene: POU2AF1 was added gene: POU2AF1 was added to Mendeliome. Sources: Expert Review Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POU2AF1 were set to 33571536 Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related Review for gene: POU2AF1 was set to RED Added comment: Single individual from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers. Sources: Expert Review |
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Mendeliome v0.14742 | DSPP | Zornitza Stark Phenotypes for gene: DSPP were changed from to Deafness, autosomal dominant 39, with dentinogenesis - MIM#605594; Dentin dysplasia, type II - MIM#125420; Dentinogenesis imperfecta, Shields type II - MIM#125490; Dentinogenesis imperfecta, Shields type III - MIM#125500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.14740 | DUOX2 | Zornitza Stark Phenotypes for gene: DUOX2 were changed from to Thyroid dyshormonogenesis 6 - MIM#607200 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.14738 | DUOXA2 | Zornitza Stark Phenotypes for gene: DUOXA2 were changed from to Thyroid dyshormonogenesis 5 - MIM#274900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.14291 | DNAJC3 | Krithika Murali changed review comment from: Well-established association with monogenic diabetes with growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families).; to: Well-established association with monogenic diabetes. Growth restriction, hypothyroidism, neuropathy, sensorineural hearing loss and cerebellar ataxia also reported in affected individuals (PMID 33486469 Lytrvi et al 2021 report 2 additional families and summarise the phenotypic features of 4 previously reported families). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.14029 | FGG | Bryony Thompson Phenotypes for gene: FGG were changed from to congenital fibrinogen deficiency MONDO:0018060 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.14024 | FGG | Bryony Thompson reviewed gene: FGG: Rating: GREEN; Mode of pathogenicity: None; Publications: 2713997, 11001902, 11001903, 9746756, 23560673, 28992465, 10980108, 15304068; Phenotypes: congenital fibrinogen deficiency MONDO:0018060; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13991 | DSPP | Krithika Murali reviewed gene: DSPP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 39, with dentinogenesis - MIM#605594, Dentin dysplasia, type II - MIM#125420, Dentinogenesis imperfecta, Shields type II - MIM#125490, Dentinogenesis imperfecta, Shields type III - MIM#125500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13991 | DUOX2 | Krithika Murali reviewed gene: DUOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 6 - MIM#607200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13991 | DUOXA2 | Krithika Murali reviewed gene: DUOXA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid dyshormonogenesis 5 - MIM#274900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13684 | CORIN | Ain Roesley Added comment: Comment on list classification: pre-eclampsia is typically not monogenic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13103 | FAM58A | Bryony Thompson Phenotypes for gene: FAM58A were changed from to syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.13100 | FAM58A | Bryony Thompson reviewed gene: FAM58A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18297069, 8818947, 28322501, 8818947; Phenotypes: syndactyly-telecanthus-anogenital and renal malformations syndrome MONDO:0010408; Mode of inheritance: Other; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.12373 | SLC6A19 | Zornitza Stark Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, MIM# 234500; Hyperglycinuria, MIM# 138500; Iminoglycinuria, MIM# 242600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.12186 | TG | Zornitza Stark Phenotypes for gene: TG were changed from to Thyroid dyshormonogenesis 3, MIM# 274700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.12183 | TG | Zornitza Stark reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: 33832185, 19169491, 28620499, 18631008, 12915634; Phenotypes: Thyroid dyshormonogenesis 3, MIM# 274700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11880 | NOG | Zornitza Stark Marked gene: NOG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11880 | NOG | Zornitza Stark Gene: nog has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11880 | NOG | Zornitza Stark Phenotypes for gene: NOG were changed from to Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11879 | NOG | Zornitza Stark Publications for gene: NOG were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11878 | NOG | Zornitza Stark Mode of inheritance for gene: NOG was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11860 | NOG | Krithika Murali reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 11846737, 18440889, 12089654, 10080184, 15066478, 22088931, 17381491; Phenotypes: Brachydactyly, type B2 - MIM#611377, Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11365 | IYD | Zornitza Stark Phenotypes for gene: IYD were changed from to Thyroid dyshormonogenesis 4, MIM# 274800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11362 | IYD | Zornitza Stark reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: 18434651, 18434651; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.11097 | HIST1H4F |
Elena Savva gene: HIST1H4F was added gene: HIST1H4F was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HIST1H4F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4F were set to PMID: 35202563 Phenotypes for gene: HIST1H4F were set to Neurodevelopmental disorders Review for gene: HIST1H4F was set to AMBER Added comment: PMID: 35202563 - single de novo missense in a patient with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay. - zebrafish studies show a significant increase in all of mild dev delay, necrosis, defective organogenesis and pre-gastrulation failure Sources: Literature |
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Mendeliome v0.11092 | HIST1H4I |
Elena Savva gene: HIST1H4I was added gene: HIST1H4I was added to Mendeliome. Sources: Literature Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HIST1H4I were set to PMID: 35202563 Phenotypes for gene: HIST1H4I were set to Neurodevelopmental syndrome Review for gene: HIST1H4I was set to GREEN Added comment: PMID: 35202563 - 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands. - Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis. - All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms. - 2/3 patients showed bilateral conductive hearing loss Sources: Literature |
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Mendeliome v0.10244 | SEMA7A |
Paul De Fazio changed review comment from: There is no conclusive evidence of association with monogenic disease for this gene. Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women. Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell. Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.; to: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women. Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell. Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype. Low evidence for association with disease. |
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Mendeliome v0.8968 | BLM | Zornitza Stark Phenotypes for gene: BLM were changed from to Bloom Syndrome MIM# 210900; Short stature, dysmorphic facies; sun-sensitive; immunoglobulin deficiency (IgA, IgG, IgM); erythema; marrow failure; leukaemia; lymphoma; chromosomal instability; predisposition to malignancies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8953 | BLM | Danielle Ariti reviewed gene: BLM: Rating: GREEN; Mode of pathogenicity: None; Publications: 17407155, 9285778, 7585968, 8079989, 12242442, 11101838; Phenotypes: Bloom Syndrome MIM# 210900, Short stature, dysmorphic facies, sun-sensitive, immunoglobulin deficiency (IgA, IgG, IgM), erythema, marrow failure, leukaemia, lymphoma, chromosomal instability, predisposition to malignancies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8644 | MAP3K14 | Zornitza Stark Phenotypes for gene: MAP3K14 were changed from to NIK deficiency; Poor T cell proliferation to antigen; Low B-cell numbers; Low NK number and function; recurrent bacterial/viral/ cryptosporidium infections; hypogammaglobulinaemia; decreased immunoglobulin levels | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8641 | MAP3K14 | Zornitza Stark reviewed gene: MAP3K14: Rating: GREEN; Mode of pathogenicity: None; Publications: 10319865, 11238593, 12352969; Phenotypes: NIK deficiency, Poor T cell proliferation to antigen, Low B-cell numbers, Low NK number and function, recurrent bacterial/viral/ cryptosporidium infections, hypogammaglobulinaemia, decreased immunoglobulin levels; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8629 | IL7R | Zornitza Stark Phenotypes for gene: IL7R were changed from to Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8614 | IL7R | Danielle Ariti reviewed gene: IL7R: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843216, 19890784, 26123418, 11023514, 7964471; Phenotypes: Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971, fever, rash, failure to thrive, recurrent respiratory and gastric infections, diarrhoea, lymphadenopathy, pneumonitis, Pancytopaenia, low T-cell numbers, decreased immunoglobulins, normal-high B/NK-cell numbers.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8527 | DNMT3B | Zornitza Stark Phenotypes for gene: DNMT3B were changed from to Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.8524 | DNMT3B | Zornitza Stark reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20587527, 10555141, 17359920, 9718351, 10647011, 11102980, 12239717; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860, facial dysmorphic features, flat nasal bridge, developmental delay, macroglossia, bacterial/opportunistic infections (recurrent), malabsorption, cytopaenia, malignancies, multiradial configurations of chromosomes 1, 9, 16, Hypogammaglobulinaemia, agammaglobulinaemia, variable antibody deficiency, decreased immunoglobulin production, low T/B/NK cells; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7905 | PLG |
Zornitza Stark changed review comment from: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder. Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. At least 3 unrelated families reported.; to: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder. Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. Over 20 unrelated families reported. |
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Mendeliome v0.7905 | PLG | Zornitza Stark Phenotypes for gene: PLG were changed from to Hereditary angioedema-4 (HAE4), MIM#619360; Plasminogen deficiency, type I, MIM# 217090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7902 | PLG | Zornitza Stark reviewed gene: PLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 28795768, 29548426, 29987869, 9242524, 10233898; Phenotypes: Hereditary angioedema-4 (HAE4), MIM#619360, Plasminogen deficiency, type I, MIM# 217090; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7820 | SERPINE1 | Zornitza Stark Phenotypes for gene: SERPINE1 were changed from to Plasminogen activator inhibitor-1 deficiency, MIM# 613329 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7817 | SERPINE1 | Zornitza Stark reviewed gene: SERPINE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9207454, 15650551; Phenotypes: Plasminogen activator inhibitor-1 deficiency, MIM# 613329; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7770 | FGB | Zornitza Stark Phenotypes for gene: FGB were changed from to Afibrinogenaemia, congenital, MIM# 202400; Hypofibrinogenaemia, congenital, MIM# 202400; Dysfibrinogenaemia, congenital, MIM# 616004 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7767 | FGB |
Zornitza Stark changed review comment from: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both. Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder. Well established gene-disease association.; to: Inherited disorders of fibrinogen affect either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenemia) of the circulating fibrinogen or both. Afibrinogenaemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenaemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial haemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. First-trimester pregnancy loss is common. Both arterial and venous thromboembolic complications have been reported. Hypofibrinogenaemia is a milder disorder. Well established gene-disease association. |
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Mendeliome v0.7767 | FGB | Zornitza Stark reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: 12393540, 16195396; Phenotypes: Afibrinogenaemia, congenital, MIM# 202400, Hypofibrinogenaemia, congenital, MIM# 202400, Dysfibrinogenaemia, congenital, MIM# 616004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7640 | FGA | Zornitza Stark Phenotypes for gene: FGA were changed from to Afibrinogenemia, congenital (MIM#202400), AR; Amyloidosis, familial visceral (MIM#105200), AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7637 | FGA | Chern Lim reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31064749, 17295221, 19073821, 11739173; Phenotypes: Afibrinogenemia, congenital (MIM#202400), AR, Amyloidosis, familial visceral (MIM#105200), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7626 | SLCO1B1 | Zornitza Stark Added comment: Comment when marking as ready: Not a monogenic disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7509 | PTPN4 |
Bryony Thompson gene: PTPN4 was added gene: PTPN4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PTPN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTPN4 were set to 17953619; 25424712; 30238967; DOI: https://doi.org/10.1016/j.xhgg.2021.100033 Phenotypes for gene: PTPN4 were set to Intellectual disability; developmental delay Review for gene: PTPN4 was set to GREEN Added comment: >3 unrelated probands and supporting mouse model PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo. Sources: Literature |
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Mendeliome v0.7147 | MIA3 |
Zornitza Stark changed review comment from: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported. Mouse model has absence of bone mineralization. Sources: Expert list; to: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Sources: Expert list |
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Mendeliome v0.7147 | MIA3 |
Zornitza Stark gene: MIA3 was added gene: MIA3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to 32101163; 33778321 Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269 Review for gene: MIA3 was set to AMBER Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported. Mouse model has absence of bone mineralization. Sources: Expert list |
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Mendeliome v0.7121 | SLC5A5 | Zornitza Stark Phenotypes for gene: SLC5A5 were changed from to Thyroid dyshormonogenesis 1, MIM# 274400; MONDO:0020716 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.7118 | SLC5A5 | Zornitza Stark reviewed gene: SLC5A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9745458, 9171822, 33815280, 32319661; Phenotypes: Thyroid dyshormonogenesis 1, MIM# 274400, MONDO:0020716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.6289 | SLC36A2 | Zornitza Stark Phenotypes for gene: SLC36A2 were changed from to Hyperglycinuria MIM#138500; Iminoglycinuria, digenic MIM#242600; Disorders of amino acid transport | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.6285 | SLC36A2 | Zornitza Stark reviewed gene: SLC36A2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19033659, 26141664, 27604308; Phenotypes: Hyperglycinuria MIM#138500, Iminoglycinuria, digenic MIM#242600, Disorders of amino acid transport; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.6107 | CREB3L3 |
Bryony Thompson gene: CREB3L3 was added gene: CREB3L3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694 Phenotypes for gene: CREB3L3 were set to Hyperlipidaemia; hypertriglyceridemia Review for gene: CREB3L3 was set to AMBER Added comment: PMID: 26427795 - a loss of function variant (c.359delG p.K120fsX20) was identified in 2 affected adult siblings and a 13 yo normotriglyceridemic daughter of one of the siblings. PMID: 21666694 - Lipoprotein profiles of the families of 4 individuals with CREB3L3 nonsense mutations showed a significantly elevated mean plasma TG level in 11 mutation carriers compared with 5 non-carrier first-degree relatives (9.67 ± 4.70 vs. 1.66 ± 0.55 mM, P = 0.021, Wilcoxon test). 3 of those families have the same variant - Lys245GlufsTer130, which has 126 (281,946 alleles) hets in gnomAD v2.1. PMID: 32580631 - case-control analysis of nonmonogenic severe hypertriglyceridemia cases (N=265) vs normolipidemic controls (N=477), identified 5 cases with LoF variants (3 of whom had the Lys245GlufsTer130 frameshift) and none in controls. OR 20.2 (95% CI 1.11–366.1) p = 0.002, adjusted p = 0.03. The frequency of Lys245GlufsTer130 is higher than expected for a dominant disorder, but other loss of function variants have been identified. The gene may be associated with variable penetrance. There are multiple supporting null mouse models with hyperlipidaemia. Sources: Expert list |
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Mendeliome v0.5174 | TPO | Zornitza Stark Phenotypes for gene: TPO were changed from to Thyroid dyshormonogenesis 2A, MIM# 274500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.5171 | TPO | Zornitza Stark reviewed gene: TPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 8027236, 10084596; Phenotypes: Thyroid dyshormonogenesis 2A, MIM# 274500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.4229 | TET2 | Zornitza Stark changed review comment from: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.; to: Mono-allelic variants: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.2787 | TET2 | Zornitza Stark edited their review of gene: TET2: Added comment: Association study (PMID 32330418) found enrichment of non-coding and LoF TET2 variants in cohort of individuals with early onset dementia, unclear if this is monogenic or polygenic contribution.; Changed publications: 30890702, 31827242, 32330418 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.2767 | UGDH |
Zornitza Stark gene: UGDH was added gene: UGDH was added to Mendeliome. Sources: Literature Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGDH were set to 32001716 Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792 Review for gene: UGDH was set to GREEN Added comment: 36 individuals with biallelic UGDH pathogenic variants reported. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode. UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate). Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors Sources: Literature |
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Mendeliome v0.2361 | USP45 |
Kristin Rigbye gene: USP45 was added gene: USP45 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: USP45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: USP45 were set to 30573563 Phenotypes for gene: USP45 were set to Leber congenital amaurosis; retinal dystrophy Review for gene: USP45 was set to GREEN Added comment: 2 unrelated Chinese families reported with rare homozygous variants (one missense, one nonsense) and Leber congenital amaurosis. Animal knockout functional studies supported gene-disease association. PMID: 30573563 "By analysing WES data based on allele frequencies of in-house controls, population allele frequencies and in silico prediction tools, two rare homozygous mutations in USP45 were identified in two unrelated families. Immunohistochemistry of USP45 in the human and zebrafish retinal sections revealed enriched expression in the inner segments of photoreceptors. The knockdown of usp45 transcript in zebrafish led to abnormal retinal development with effects on photoreceptors, which could be successfully rescued by wild-type usp45 mRNA. Moreover, targeted knockout of Usp45 in mice caused abnormal electroretinography responses, similar to that seen in patients with LCA." Sources: Literature |
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Mendeliome v0.2161 | TNFSF12 | Zornitza Stark Phenotypes for gene: TNFSF12 were changed from to Recurrent infections, poor antibody responses, decreased immunoglobulins | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.2157 | TNFSF12 | Zornitza Stark reviewed gene: TNFSF12: Rating: RED; Mode of pathogenicity: None; Publications: 23493554; Phenotypes: Recurrent infections, poor antibody responses, decreased immunoglobulins; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.1850 | FBN2 | Zornitza Stark Added comment: Comment when marking as ready: The gene-disease association with Contractual arachnodactyly is extremely well established. The gene-disease association with macular degeneration much less so. There are ~4 families reported in the literature, and some discussion about whether the contribution of rare FBN2 variants in this context are under a 'monogenic' or 'polygenic' model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mendeliome v0.0 | NOG |
Zornitza Stark gene: NOG was added gene: NOG was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: NOG was set to Unknown |