Bleeding and platelet disorders

Gene: BLOC1S5

This gene is associated with a phenotype in OMIM but not Gene2Phenotype. Based on the new reports there is now enough evidence for this gene to be promoted to Green. This gene should be promoted to Green at the next GMS review.

Created: 7 Nov 2023, 1:17 p.m. | Last Modified: 7 Nov 2023, 1:17 p.m.

Panel Version: 3.7

Green List (high evidence)

Two more reports of patients with HPS due to BLOC1S5 mutations
PMID 34685610 - two siblings from a consanguinous family with a homozygous novel mutation
PMID 34058075 - one patient with a homozygous novel mutation, parents both confirmed as carriers

Created: 15 Aug 2023, 3:39 p.m. | Last Modified: 15 Aug 2023, 3:39 p.m.

Panel Version: 3.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 34685610
• 34058075

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 4:48 p.m. | Last Modified: 5 Dec 2024, 4:48 p.m.

Panel Version: 3.12

Comment on list classification: Two unrelated patients with this mild form of HPS. Rating Amber awaiting further publications with additional cases or clinical evidence supporting this gene-disease association.

Created: 7 Oct 2020, 11:35 a.m. | Last Modified: 7 Oct 2020, 11:35 a.m.

Panel Version: 1.12

- PMID: 32565547 (2020) - Patient 1 (20 years old) was initially diagnosed only with oculocutaneous albinism, but secondarily reported mild bleeding diathesis characterised by easy bruising and infrequent episodes of epistaxis and gingival bleeding. Patient 2 (39 years old) reported menorrhagia and excessive blood loss after deliveries and surgery. Further analyses documented in both patients a lack of detectable platelet dense granules, concomitant with mildly impaired activation-induced ATP release and platelet aggregation in vitro.

Created: 7 Oct 2020, 11:22 a.m. | Last Modified: 7 Oct 2020, 11:22 a.m.

Panel Version: 1.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky–Pudlak syndrome

Publications

• 32565547

Green List (high evidence)

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

Created: 5 Oct 2020, 9:11 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky–Pudlak syndrome

Publications

• 32565547

Variants in this GENE are reported as part of current diagnostic practice