This report includes information relevant to a potential model of Hermansky-Pudlak syndrome 7 (HPS7), which is a subtype of Hermansky-Pudlak syndrome; HPS7 exhibits autosomal recessive inheritance. The human gene implicated in this disease is DTNBP1, which encodes dystrobrevin binding protein 1 (or dysbindin), a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC1) that plays a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. There is one high-scoring fly ortholog, Dysb, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical alleles have been generated. DTNBP1 has also been associated with schizophrenia (MIM:181500, FBhh0000528).
For multiple subtypes of Hermansky-Pudlak syndrome, the implicated gene encodes a subunit of a BLOC complex, in this case the BLOC1 complex.
A UAS construct of a wild-type human Hsap\DTNBP1 gene has been introduced into flies, but has not yet been analyzed in the context of Hermansky-Pudlak syndrome. Partial heterologous rescue (functional complementation) has been observed for phenotypes of a hypomorphic mutation of Dmel\Dysb.
[updated Jul. 2019 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]
[HERMANSKY-PUDLAK SYNDROME 7; HPS7](https://omim.org/entry/614076)
[DYSTROBREVIN-BINDING PROTEIN 1; DTNBP1](https://omim.org/entry/607145)
See description of Hermansky-Pudlak syndrome, above.
Hermansky-Pudlak syndrome-7 (HPS7) is caused by homozygous mutation in DTNBP1, the gene encoding dystrobrevin binding protein 1 (or dysbindin), subunit 8 of the BLOC1 complex. [From MIM:614076 and MIM:607145, 2016.04.11]
In a mouse model, the dysbindin protein has been shown to be important for normal platelet-dense granule and melanosome biogenesis. (Li et al., 2003, pubmed:12923531). [From MIM:614076, 2016.04.11]
DTNBP1 encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). [provided by RefSeq, Jul 2008]
The DTNBP1 gene encodes dysbindin, a key component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), which regulates the trafficking of proteins in the lysosomal pathway (summary by Tang et al., 2009, pubmed:19955431). [From MIM:607145, 2016.04.11]
One to one: 1 human to 1 Drosophila.
