Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.

We report a Japanese man with Hermansky-Pudlak syndrome, having oculocutancous 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 ( 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 mieroscopy 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 ending 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.