Characterization of melanosomes and melanin in Japanese patients with Hermansky-Pudlak syndrome types 1, 4, 6, and 9
Characterization of melanosomes and melanin in Japanese patients with Hermansky-Pudlak syndrome types 1, 4, 6, and 9
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DOI：
10.1111/pcmr.12662
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发表时间：
2018-03-01
影响因子：
4.3
通讯作者：
Suzuki, Tamio
中科院分区：
文献类型：
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作者：
Okamura, Ken;Abe, Yuko;Suzuki, Tamio
Hermansky-Pudlak综合征（HPS）是一种常染色体隐性遗传疾病，以眼皮肤白化病（OCA）、出血倾向和蜡样物质沉积为特征。大多数HPS致病基因编码溶酶体相关细胞器复合物（BLOC）生物合成的亚基。在这项研究中，我们通过全外显子组测序确定了HPS 4，HPS 6和HPS 9各一名患者。接下来，我们使用电子显微镜和化学方法分析了三名患者和代表性HPS 1患者和对照组的头发样本。与健康对照组相比，所有HPS患者的黑素体更少、更小、更不成熟。此外，所有患者均显示总黑色素含量降低和苯并噻嗪型褐黑素水平升高。这项研究的结果表明，通过对他们的头发样本的分析，BLOC的功能障碍对黑色素体的成熟和黑色素水平和组成的影响。
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome-related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6, and HPS9 by whole-exome sequencing. Next, we analyzed hair samples from the three patients and representative patients with HPS1 and controls using electron microscopy and chemical methods. All HPS patients had fewer, smaller, and more immature melanosomes than healthy controls. Further, all patients showed reduced total melanin content and increased levels of benzothiazine-type pheomelanin. The results of this study demonstrate the impact of the dysfunctions of BLOCs on the maturation of melanosomes and melanin levels and composition through analysis of their hair samples.