PDF(Pubmed)
Abstract：
Hermansky-Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by oculocutaneous albinism (OCA) and bleeding diathesis. To date, 11 HPS types have been reported (HPS-1 to HPS-11), each defined by disease-causing variants in specific genes. Variants in the HPS1 gene were found in approximately 15% of HPS patients, most of whom harbor the Puerto Rican founder mutation. In this study, we report six affected individuals from three nonconsanguineous families of Ashkenazi Jewish descent, who presented with OCA and multiple ecchymoses and had normal platelet number and size. Linkage analysis indicated complete segregation to HPS3. Sequencing of the whole coding region and the intron boundaries of HPS3 revealed a heterozygous c.1163+1G>A variant in all six patients. Long-range PCR amplification revealed that all affected individuals also carry a 14,761bp deletion that includes the 5\'UTR and exon 1 of HPS3, encompassing regions with long interspersed nuclear elements. The frequency of the c.1163+1G>A splice site variant was found to be 1:200 in the Ashkenazi Jewish population, whereas the large deletion was not detected in 300 Ashkenazi Jewish controls. These results present a novel HPS3 deletion mutation and suggest that the prevalence of HPS-3 in Ashkenazi Jews is more common than previously thought.
摘要：
Hermansky-Pudlak综合征（HPS）是一组罕见的常染色体隐性遗传疾病，其特征是眼皮肤白化病（OCA）和出血素质。迄今为止,已报告11种HPS类型（HPS-1至HPS-11），每个由特定基因的致病变异定义。在大约15%的HPS患者中发现了HPS1基因的变异，他们中的大多数人都有波多黎各创始人的突变。在这项研究中,我们报告了来自三个阿什肯纳齐犹太血统的非近亲家庭的六个受影响的个体，患者出现OCA和多个瘀斑，血小板数量和大小正常。连锁分析表明与HPS3完全分离。HPS3的整个编码区和内含子边界的测序揭示了所有六名患者中的杂合c.1163+1G>A变体。远程PCR扩增显示，所有受影响的个体还携带一个14,761bp的缺失，其中包括HPS3的5'UTR和外显子1，涵盖具有长散布核元件的区域。在Ashkenazi犹太人口中，c.11631G>A剪接位点变异的频率为1:200，而在300名Ashkenazi犹太人对照中未检测到大缺失。这些结果提出了一种新的HPS3缺失突变，并表明HPS-3在德系犹太人中的流行比以前认为的更为普遍。
