Hermansky-Pudlak综合征1型(HPS1)在日本白化病患者中频发和HPS1突变蛋白的功能分析  

High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein

作　　者：Ito S. Suzuki T. Inagaki K. 任建文 

机构地区：[1]Department of Dermatology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466- 8550, Japan Dr.

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2006年第8期13-13,共1页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism(OCA), bleeding tendency, and lysosomal accumulation of ceroid-like material. Seven genetically distinct subtypes of HPS are known in humans; most are rare outside of Puerto Rico. Here, we describe the analysis of the HPS1 gene in 24 Japanese OCA patients who lacked mutations in the four genes known to cause OCA (TYR/OCA1, P/OCA2, TVRP1/OCA3, and MATP/OCA4), and the identification of eight different HPS1 mutations in ten of these patients, four of which were novel (W583X,L668P, 532insC,1691delA).An IVS5 + 5G→ A splice consensus mutation was particularly frequent, the result of a founder effect for this allele in Japanese patients. Functional analysis by transfection of the L668P variant into Hps1-mutant melanep mouse melanocytes showed that this missense substitution is pathologic, resulting in an Hps-1 protein that is unable to assemble into the biogenesis of lysosome-related organelles complex-3.Hermansky-Pudlak syndrome （HPS） is an autosomal recessive disorder characterized by oculocutaneous albinism （OCA）, bleeding tendency, and lysosomal accumulation of ceroid-like material. Seven genetically distinct subtypes of HPS are known in humans; most are rare outside of Puerto Rico. Here, we describe the analysis of the HPS1 gene in 24 Japanese OCA patients who lacked mutations in the four genes known to cause OCA （TYR/OCA1, P/OCA2, TVRP1/OCAS, and MATP/OCA4）, and the identification of eight different HPS1 mutations in ten of these patients, four of which were novel （W585X, L668P, 532insC, 1691delA）. An IVS5 ＋ 5G→A splice consensus mutation was particularly frequent, the result of a founder effect for this allele in Japanese patients. Functional analysis by transfection of the L668P variant into Hpsl-mutant melanep mouse melanocytes showed that this missense substitution is pathologic,

关 键 词：Hermansky-Pudlak综合征 眼皮肤白化病 突变蛋白 患者 日本 常染色体隐性遗传病 基因分析 体内沉积 

分 类 号：R758.54[医药卫生—皮肤病学与性病学] R758.4[医药卫生—临床医学]