Horikawa T, Araki K, Fukai K, Ueda M, Ueda T, Ito S, Ichihashi M
Department of Dermatology, Kobe University School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe 650-0017, Japan.
Br J Dermatol. 2000 Sep;143(3):635-40. doi: 10.1111/j.1365-2133.2000.03725.x.
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.
我们报告了一名患有Hermansky-Pudlak综合征的日本男性，其患有眼皮肤白化病并伴有出血倾向。对该患者外周血细胞进行基因分析发现，他是HPS1基因突变的复合杂合子。其中一个突变是外显子11中第321密码子处的一个新的移码突变（插入一个G，即962 - 963insG），另一个是内含子5的5'剪接连接突变（IVS5 + 5G→A）。该患者毛发中的真黑素含量显著降低。用光镜和电镜进行的组织学分析显示，患者表皮中的黑素细胞含有相当数量的巨大黑素小体。来自患者皮肤的培养黑素细胞也含有巨大黑素小体。我们关于HPS1基因突变与黑素小体形态和黑色素生成异常相关的发现，揭示了HPS1基因产物在黑素小体和黑色素合成中的作用和功能。
