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| Bleeding and platelet disorders v2.4 | 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 v1.38 | MPL | Arina Puzriakova Phenotypes for gene: MPL were changed from 604498 Thrombocytopenia, congenital amegakaryocytic to Thrombocytopenia, congenital amegakaryocytic, OMIM:604498 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| Bleeding and platelet disorders v0.77 | PTPN11 |
Louise Daugherty edited their review of gene: PTPN11: Added comment: During the GMS Haematology Specialist Test Group webex call 8th March 2019 it was agreed to demote PRPN11 from Green to Red based on the syndromic phenotype (Noonan syndrome) would not present as bleeding/thrombocytopenia without other obvious symptoms. Subsequent to this, a detailed review was recieved from Andrew Mumford (16th September 2019) : The clinical utility of the panel is to aid diagnosis of people presenting with bleeding or platelet disorders, where laboratory phenotype testing is insufficient for diagnosis. Noonan syndrome is about twice as common as haemophilia A, and can definitely present with coagulopathy with other features incompletely expressed of not recognised. These are all arguments to include PTPN11. Discovering Noonan syndrome is clinically important because of potential in interventions for other occult clinical features , like cardiac disease. However, we also have to be pragmatic here because using the same argument, there are dozens genes for other syndromic disorders which may present as a first contact in the bleeding disorders clinic (eg the EDS genes, CDG genes). We obviously shouldn’t be looking at all of these. The sensible option to me is to place carefully selected genes in this class ( i. associated with ‘common’ disorders and ii. in which other syndromic features may be less obvious to non-geneticists). After this review, the gene was discussed again, and Carl Fratter and other members of the Haematology Specialist Test Group (Mandy Nesbit, Steve Keeny, Nicola Curry, Mike Mitchell agreed to change PTPN11 from Red to Amber rating, as this would then be in line with the Amber EDS genes on this panel.; Changed rating: AMBER |
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| Bleeding and platelet disorders v0.69 | COL3A1 |
Louise Daugherty commented on gene: COL3A1: Discussed further with the GMS Haematology Specialist Test Group at workshop 2nd July 2019, it was agreed that Carl Fratter would review the evidence on COL3A1 by contacting their Thrombogenomics team to ask if they are able to provide any information on their experience, as they have included these genes in their panel. Gene rating to be confirmed when group has this information. Carl Fratter has since highlighted a report (PMID: 30690834) with a family with COL3A1 who presented with bruising (prepositus/family 3), noting it’s complicated by the fact that they are reporting it because of a VWF variant of uncertain significance (which is quite common in the general population, and so perhaps not likely to be very significant), but does appear to be an example of COL3A1 related EDS which was not obvious clinically and patient was referred for easy bruising before EDS was diagnosed. Awaiting consensus from the GMS Haematology Specialist Test Group regarding this |
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| Bleeding and platelet disorders v0.28 | MPL | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.28 | MPL | Louise Daugherty commented on gene: MPL: 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: MPL; Suggested initial 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: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.27 | MPL | Steve Keeney reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.26 | MPL | Louise Daugherty Added phenotypes 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.24 | MPL | Louise Daugherty Source North West GLH was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.23 | MPL | Louise Daugherty commented on gene: MPL: 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: MPL; 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: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.22 | MPL | Mandy nesbitt reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.21 | MPL | Louise Daugherty Added phenotypes 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.19 | MPL | Louise Daugherty Source Yorkshire and North East GLH was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.14 | MPL | Louise Daugherty commented on gene: MPL: 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: MPL; 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: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.10 | MPL | Louise Daugherty commented on gene: MPL: 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: MPL; 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: 604498 Thrombocytopenia, congenital amegakaryocytic; PMID(s): none submitted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.9 | MPL | Michael Mitchell reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 604498 Thrombocytopenia, congenital amegakaryocytic; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.8 | MPL | Louise Daugherty Added phenotypes 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.7 | MPL | Louise Daugherty Source London South GLH was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.6 | MPL | Louise Daugherty reviewed gene: MPL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.5 | MPL | Carl Fratter reviewed gene: MPL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: ; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.4 | MPL | Louise Daugherty Source NHS GMS was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.3 | MPL |
Louise Daugherty Source Expert Review Green was added to MPL. Mode of inheritance for gene MPL was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes 604498 Thrombocytopenia, congenital amegakaryocytic for gene: MPL Publications for gene MPL were changed from to 16470591; 11133753; 22180433 Rating Changed from Red List (low evidence) to Green List (high evidence) |
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| Bleeding and platelet disorders v0.2 | MPL |
Louise Daugherty gene: MPL was added gene: MPL was added to Bleeding and platelet disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: MPL was set to |
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