This report describes general characteristics of the group of diseases classified as Hermansky-Pudlak syndrome. Hermansky-Pudlak syndrome is a genetically heterogeneous disorder, with multiple genes and mapped loci. Hermansky-Pudlak syndrome subtypes are associated with autosomal recessive mutations in genes encoding members of protein complexes involved with endosomal protein sorting machinery, including the adaptor protein 3 (AP3) complex, and the three biogenesis of lysome-related organelles complexes (BLOC1, BLOC2, and BLOC3). A listing of Hermansky-Pudlak syndrome subtypes, as defined by OMIM, may be found in the table below, with links to more detailed reports for subtypes that have been investigated using fly models.
[updated April 2016 by FlyBase; FBrf0222196]
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 (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 subtypes are associated with autosomal recessive mutations in genes encoding members of protein complexes involved with endosomal protein sorting machinery.
Hermansky-Pudlak syndrome-associated protein complexes involved in endosomal protein-sorting machinery include the adaptor protein complex 3 (AP3, FBgg0000136), a heterotetrameric complex that includes the protein encoded by the gene associated with HPS2 (MIM:608233); the biogenesis of lyosome-related organelles complex (BLOC)-1 (BLOC-1), an octamer whose components include proteins encoded by the genes associated with HPS7 (MIM:614076), HPS8 (MIM:614077) and HPS9 (MIM:614071); BLOC-2, a heterotrimer whose components include the proteins encoded by the genes associated with HPS3 (MIM:614072), HPS5 (MIM:614074) and HPS6 (MIM:614075; and BLOC-3, a complex whose components include the proteins encoded by the genes associated with HPS1 (MIM:203300) and HPS4 (MIM:614073) (Cheli and Dell'Angelica, 2010, FBrf0223278; and reviewed in Cheli, et al., 2010, FBrf0209903).
