This report describes Hermansky-Pudlak syndrome, Blos1-related. This disease, which has been modeled in flies but not yet reported in human patients, is a proposed subtype of Hermansky-Pudlak syndrome. The fly gene associated with this disease model is Blos1, which is the only high-scoring fly ortholog of the human gene BLOC1S1, a member of the BLOC1 complex; several other human genes encoding the proteins comprising this complex are implicated in other Hermansky-Pudlak syndrome subtypes. RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical alleles of Blos1 have been generated.
For multiple subtypes of Hermansky-Pudlak syndrome, the implicated gene encodes a subunit of a BLOC complex, in this case the BLOC1 complex.
The human gene BLOC1S1 has not been introduced into flies.
For loss-of-function mutations in the Dmel\Blos1 gene, observed phenotypes include aspects similar to those observed in Hermansky-Pudlak syndrome subtypes associated with mutations in BLOC1 complex genes, including pigmentation defects in the eye. Physical and genetic interactions of Dmel\Blos1 have been described; see below and in the Blos1 gene report.
See also the human disease model report for 'schizophrenia, susceptibility to (postulated), BLOC1S1-related' (FBhh0000527).
[updated Jul. 2017 by FlyBase; FBrf0222196]
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes (Oh et al., 1998, pubmed:9497254). [from MIM:115200, 2016.03.25]
Hermansky-Pudlak syndrome (HPS) is a multisystem disorder characterized by: tyrosinase-positive oculocutaneous albinism; a bleeding diathesis resulting from a platelet storage pool deficiency; and, in some cases, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The albinism is characterized by: hypopigmentation of the skin and hair; and ocular findings of reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in easy bruising, frequent epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects are associated primarily with HPS-2. [from GeneReviews, Hermansky-Pudlak Syndrome, pubmed:20301486 2016.01.26]
One to one: 1 human to 1 Drosophila.
Ortholog of human BLOC1S1 (1 Drosophila to 1 human).
Dmel\Blos1 shares 58% identity and 76% similarity with human BLOC1S1.
