| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bleeding and platelet disorders v1.9 | BLOC1S5 |
Zornitza Stark gene: BLOC1S5 was added gene: BLOC1S5 was added to Bleeding and platelet disorders. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome 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 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.28 | BLOC1S6 | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.28 | BLOC1S6 | Louise Daugherty commented on gene: BLOC1S6: Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: BLOC1S6; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.27 | BLOC1S6 | Steve Keeney reviewed gene: BLOC1S6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.26 | BLOC1S6 | Louise Daugherty Added phenotypes 614171 ?Hermansky-pudlak syndrome 9 for gene: BLOC1S6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.24 | BLOC1S6 | Louise Daugherty Source North West GLH was added to BLOC1S6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.23 | BLOC1S6 | Louise Daugherty commented on gene: BLOC1S6: Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: BLOC1S6; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.22 | BLOC1S6 | Mandy nesbitt reviewed gene: BLOC1S6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.21 | BLOC1S6 | Louise Daugherty Added phenotypes 614171 ?Hermansky-pudlak syndrome 9 for gene: BLOC1S6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.19 | BLOC1S6 | Louise Daugherty Source Yorkshire and North East GLH was added to BLOC1S6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.14 | BLOC1S6 | Louise Daugherty commented on gene: BLOC1S6: Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: BLOC1S6; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.10 | BLOC1S6 | Louise Daugherty commented on gene: BLOC1S6: Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: BLOC1S6; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.9 | BLOC1S6 | Michael Mitchell reviewed gene: BLOC1S6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 614171 ?Hermansky-pudlak syndrome 9; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.8 | BLOC1S6 | Louise Daugherty Added phenotypes 614171 ?Hermansky-pudlak syndrome 9 for gene: BLOC1S6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.7 | BLOC1S6 | Louise Daugherty Source London South GLH was added to BLOC1S6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.6 | BLOC1S6 | Louise Daugherty reviewed gene: BLOC1S6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.5 | BLOC1S6 | Carl Fratter reviewed gene: BLOC1S6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.4 | BLOC1S6 | Louise Daugherty Source NHS GMS was added to BLOC1S6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.3 | BLOC1S6 |
Louise Daugherty Source Expert Review Green was added to BLOC1S6. Mode of inheritance for gene BLOC1S6 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes 614171 ?Hermansky-pudlak syndrome 9 for gene: BLOC1S6 Publications for gene BLOC1S6 were changed from to 22461475; 29054114 Rating Changed from Red List (low evidence) to Green List (high evidence) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.2 | BLOC1S6 |
Louise Daugherty gene: BLOC1S6 was added gene: BLOC1S6 was added to Bleeding and platelet disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: BLOC1S6 was set to |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||