Ito Shiro, Suzuki Tamio, Inagaki Katsuhiko, Suzuki Noriyuki, Takamori Kenji, Yamada Tomoko, Nakazawa Mitsuru, Hatano Michihiro, Takiwaki Hirotsugu, Kakuta Yumi, Spritz Richard A, Tomita Yasushi
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Invest Dermatol. 2005 Oct;125(4):715-20. doi: 10.1111/j.0022-202X.2005.23884.x.
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, TYRP1/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 melan-ep 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综合征（HPS）是一种常染色体隐性疾病，其特征为眼皮肤白化病（OCA）、出血倾向以及类蜡样物质在溶酶体中的蓄积。人类已知HPS有7种基因不同的亚型；在波多黎各以外地区，大多数都很罕见。在此，我们描述了对24名日本OCA患者HPS1基因的分析，这些患者在已知导致OCA的4个基因（TYR/OCA1、P/OCA2、TYRP1/OCA3和MATP/OCA4）中未发现突变，并在其中10名患者中鉴定出8种不同的HPS1突变，其中4种是新的（W583X、L668P、532insC、1691delA）。IVS5 + 5G→A剪接共有序列突变尤为常见，这是该等位基因在日本患者中存在奠基者效应的结果。通过将L668P变体转染到Hps1突变的黑素 - ep小鼠黑素细胞中进行功能分析，结果显示这种错义替代具有病理性，导致Hps - 1蛋白无法组装到溶酶体相关细胞器生物合成复合体3中。
