Hazelwood S, Shotelersuk V, Wildenberg S C, Chen D, Iwata F, Kaiser-Kupfer M I, White J G, King R A, Gahl W A
Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1830, USA.
Am J Hum Genet. 1997 Nov;61(5):1088-94. doi: 10.1086/301611.
Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis. In a recent report on the cloning of an HPS gene, all 22 Puerto Rican HPS patients were homozygous for a 16-bp duplication in exon 15. This presumably reflected a founder effect for the HPS mutation in Puerto Rico. Nevertheless, we ascertained two individuals from central Puerto Rico who lacked the 16-bp duplication, exhibited significant amounts of normal-size HPS mRNA by northern blot analysis, and had haplotypes in the HPS region that were different from the haplotype of every 16-bp-duplication patient. Moreover, these two individuals displayed no mutations in their cDNA sequences, throughout the entire HPS gene. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, a bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. These findings indicate that analysis of Puerto Rican patients for the 16-bp duplication in HPS cannot exclude the diagnosis of HPS. In addition, HPS most likely displays locus heterogeneity, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.
Hermansky-Pudlak综合征（HPS）包括眼皮肤白化病、血小板储存池缺陷和类蜡质脂褐质沉积症。在最近一篇关于HPS基因克隆的报告中，所有22名波多黎各HPS患者在第15外显子中均为16碱基对重复的纯合子。这大概反映了波多黎各HPS突变的奠基者效应。然而，我们确定了两名来自波多黎各中部的个体，他们没有16碱基对重复，通过Northern印迹分析显示有大量正常大小的HPS mRNA，并且在HPS区域的单倍型与每例16碱基对重复患者的单倍型不同。此外，这两名个体在整个HPS基因的cDNA序列中没有显示出突变。两名患者均表现出色素稀释、视力受损、眼球震颤、出血素质和血小板致密体缺失，从而确诊为HPS。这些发现表明，对波多黎各患者进行HPS中16碱基对重复的分析不能排除HPS的诊断。此外，HPS很可能表现出基因座异质性，这与存在几种表现出色素稀释和血小板储存池缺陷的小鼠品系一致。
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