title: Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome.
abstract: Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis that displays genetic locus heterogeneity. The eight known HPS proteins combine in functional complexes, two of which are called BLOC-2 and BLOC-3; a BLOC is a Biogenesis of Lysosome-related Organelles Complex. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times. Whole mount electron microscopy (EM) detects the absence of platelet delta granules and confirms the diagnosis of HPS. To date, the status of other organelles and granules in HPS platelets has not been documented. We performed ultrastructural studies on platelets of patients with different genetic forms of HPS, specifically those comprising the BLOC-2 and BLOC-3 subtypes. No differences in distribution, size or quantity of other platelet organelles and membrane structures could be detected in our patients. Since alpha and delta granules are formed from multivesicular bodies in the megakaryocyte, and since only delta granules are defective in HPS, we conclude that HPS genes function within the portion of delta granule biogenesis that has diverged from that of alpha granules. Thus, it is unlikely that the generalized bleeding diathesis of HPS is attributed to a deficiency of alpha granules.
authors: National Human Genome Research Institute, National Institutes of Health, Section on Human Biochemical Genetics, Medical Genetics Branch, Bethesda, MD 20892-1851, USA. mhuizing@mail.nih.gov
authors: Marjan
authors: M
authors: Huizing
authors: Jennifer M
authors: JM
authors: Parkes
authors: Amanda
authors: A
authors: Helip-Wooley
authors: James G
authors: JG
authors: White
authors: William A
authors: WA
authors: Gahl
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000473:pathology* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003594:Cytoplasmic Granules / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006470:Hemorrhage / Q000473:pathology; D022861:Hermanski-Pudlak Syndrome / Q000097:blood* / Q000145:classification / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011506:Proteins
chemical_list: C492647:BLOC1S2 protein, human; C509457:BLOC1S3 protein, human; D002352:Carrier Proteins; D011506:Proteins