Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Pigment Cell Melanoma Res. 2012 Sep;25(5):584-91. doi: 10.1111/j.1755-148X.2012.01029.x. Epub 2012 Aug 2.
Hermansky-Pudlak Syndrome (HPS) is a genetically heterogeneous disorder of lysosome-related organelle biogenesis and is characterized by oculocutaneous albinism and a bleeding diathesis. Over the past decade, we screened 250 patients with HPS-like symptoms for mutations in the genes responsible for HPS subtypes 1-6. We identified 38 individuals with no functional mutations, and therefore, we analyzed all eight genes encoding the biogenesis of lysosome-related organelles complex-1 (BLOC-1) proteins in these individuals. Here, we describe the identification of a novel nonsense mutation in BLOC1S3 (HPS-8) in a 6-yr-old Iranian boy. This mutation caused nonsense-mediated decay of BLOC1S3 mRNA and destabilized the BLOC-1 complex. Our patient's melanocytes showed aberrant localization of TYRP1, with increased plasma membrane trafficking. These findings confirm a common cellular defect for HPS patients with defects in BLOC-1 subunits. We identified only two patients with BLOC-1 defects in our cohort, suggesting that other HPS genes remain to be identified.
Hermansky-Pudlak 综合征（HPS）是一种溶酶体相关细胞器生物发生的遗传异质性疾病，其特征是眼皮肤白化病和出血倾向。在过去的十年中，我们对 250 名具有 HPS 样症状的患者进行了筛查，以寻找导致 HPS 亚型 1-6 的基因突变。我们发现了 38 名无功能突变的个体，因此，我们分析了这些个体中编码溶酶体相关细胞器生物发生复合物 1（BLOC-1）蛋白的所有 8 个基因。在这里，我们描述了在一名 6 岁的伊朗男孩中发现 BLOC1S3（HPS-8）的新型无义突变。该突变导致 BLOC1S3 mRNA 的无义介导的衰变，并使 BLOC-1 复合物不稳定。我们患者的黑素细胞显示 TYRP1 异常定位，质膜转运增加。这些发现证实了 BLOC-1 亚基缺陷的 HPS 患者存在共同的细胞缺陷。我们在队列中仅发现了两名 BLOC-1 缺陷患者，这表明还有其他 HPS 基因有待确定。
