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| Bleeding and Platelet Disorders v1.43 | PROC |
Jane Lin gene: PROC was added gene: PROC was added to Bleeding and Platelet Disorders. Sources: Expert list Mode of inheritance for gene: PROC was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PROC were set to PMID: 2437584; PMID: 7670104; PMID: 10942114; PMID: 28265398 Phenotypes for gene: PROC were set to THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT # 176860; THROMBOPHILIA DUE TO PROTEIN C DEFICIENCY, AUTOSOMAL RECESSIVE, # 612304 Review for gene: PROC was set to GREEN gene: PROC was marked as current diagnostic Added comment: Has well established gene-disease association with thrombosis. Biallelic inheritance is rare and there is evidence it is more severe but data is complicated by findings that some patients also have changes in Factor V Leiden so have not selected the option where biallelic inheritance is more severe. Sources: Expert list |
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| Bleeding and Platelet Disorders v1.16 | TLN1 |
Achchuthan Shanmugasundram gene: TLN1 was added gene: TLN1 was added to Bleeding and Platelet Disorders. Sources: Literature Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TLN1 were set to 35861643 Phenotypes for gene: TLN1 were set to thrombocytopenia, MONDO:0002049 Review for gene: TLN1 was set to RED Added comment: PMID:35861643 reported a 20-year old man of Mexican ancestry with a complex phenotype including thrombocytopenia, T lymphopenia, and low IgG levels. The patient generally had a platelet count of <20 000/mcL, but without significant bleeding. He was identified with a de novo heterozygous variant c.685C > T (p.Pro 229 Ser) that was not present in his parents. Sources: Literature |
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| Bleeding and Platelet Disorders v1.0 | SLC37A4 |
Paul De Fazio gene: SLC37A4 was added gene: SLC37A4 was added to Bleeding and Platelet Disorders. Sources: Literature Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SLC37A4 were set to 33964207 Phenotypes for gene: SLC37A4 were set to Congenital disorder of glycosylation; liver dysfunction; coagulation deficiency Review for gene: SLC37A4 was set to GREEN gene: SLC37A4 was marked as current diagnostic Added comment: 7 patients from 4 families, additional to the two reported previously, described with the same recurrent c.1267C>T (p.R423*) variant with liver dysfunction multifactorial coagulation deficiency and cardiac issues. Serum samples from affected individuals showed profound accumulation of both high mannose and hybrid type N-glycans. Hepatoma cell-line studies support the pathogenicity of the variant. Note that although most/all patients had abnormal clotting factors, only one was noted to have a history of bruising/bleeding. Sources: Literature |
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| Bleeding and Platelet Disorders v0.269 | GP9 |
Zornitza Stark edited their review of gene: GP9: Added comment: Bernard-Soulier syndrome is a bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5. At least 3 unrelated families reported, animal model.; Changed publications: 8049428, 33553065, 32030720, 31484196 |
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| Bleeding and Platelet Disorders v0.201 | BLOC1S5 |
Chirag Patel gene: BLOC1S5 was added gene: BLOC1S5 was added to Bleeding Disorders. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to PMID: 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome type 11, no OMIM# Review for gene: BLOC1S5 was set to GREEN gene: BLOC1S5 was marked as current diagnostic Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively. Sources: Literature |
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| Bleeding and Platelet Disorders v0.201 | BLOC1S5 |
Chirag Patel gene: BLOC1S5 was added gene: BLOC1S5 was added to Bleeding Disorders. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to PMID: 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome type 11, no OMIM# Review for gene: BLOC1S5 was set to GREEN gene: BLOC1S5 was marked as current diagnostic Added comment: 2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2). Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively. Sources: Literature |
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| Bleeding and Platelet Disorders v0.120 | MPL | Zornitza Stark Marked gene: MPL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.120 | MPL | Zornitza Stark Gene: mpl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.120 | MPL | Zornitza Stark Classified gene: MPL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.120 | MPL | Zornitza Stark Gene: mpl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.119 | MPL |
Zornitza Stark gene: MPL was added gene: MPL was added to Bleeding Disorders. Sources: Expert list Mode of inheritance for gene: MPL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPL were set to 11133753 Phenotypes for gene: MPL were set to Thrombocytopenia, congenital amegakaryocytic, MIM# 604498 Review for gene: MPL was set to GREEN Added comment: Well established gene-disease association. Sources: Expert list |
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