title: Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.
abstract: We report a Japanese man with Hermansky-Pudlak syndrome, having oculocutaneous albinism with a bleeding diathesis. Gene analysis of the patient's peripheral blood cells revealed that he was a compound heterozygote for HPS1 gene mutations. One of the mutations was a novel frameshift mutation at codon 321 (a G insertion) in exon 11 ( approximately 962-963insG), and the other was a 5' splice-junction mutation of IVS5 (IVS5 + 5G-->A). The content of eumelanin in the patient's hairs was significantly reduced. Histological analysis using light and electron microscopy revealed that melanocytes in the patient's epidermis contained an appreciable number of giant melanosomes. Cultured melanocytes from the patient's skin also contained giant melanosomes. Our finding of mutations in the HPS1 gene in relation to abnormalities in melanosome morphology and melanin production shed light on the role and function of the HPS1 gene product in the synthesis of melanosomes and melanin pigment.
authors.affiliation: Department of Dermatology, Kobe University School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe 650-0017, Japan. thorikaw@med.kobe-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Horikawa
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Fukai
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: T
authors.initials: T
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Ichihashi
mesh_terms: D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D016368:Frameshift Mutation / Q000235:genetics*; D015726:Giant Cells / Q000473:pathology; D006197:Hair / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D008297:Male; D008543:Melanins / Q000032:analysis; D008544:Melanocytes / Q000166:cytology; D020460:Melanosomes / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics
chemical_list: C102160:HPS1 protein, human; D008543:Melanins; D008565:Membrane Proteins