Hermansky–Pudlak syndrome type 1 in patients of Indian descent

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• 作者：Lisa M. Vincent ; David Adams ; Richard A. Hess ; Shira G. Ziegler ; Ekaterini Tsilou ; Gretchen Golas ; Kevin J. O’ ; Brien ; James G. White ; Marjan Huizing ; William A. Gahl
• 关键词：Lysosome-related organelle ; Albinism ; Indian descent ; Splice-site mutation ; Bleeding diathesis
• 刊名：Molecular Genetics and Metabolism
• 出版年：2009
• 出版时间：July 2009
• 年：2009
• 卷：97
• 期：3
• 页码：227-233
• 全文大小：2370 K

文摘

Hermansky–Pudlak syndrome (HPS) develops from defects in the biogenesis and/or function of lysosome-related organelles essential to membrane and protein trafficking. Of the eight known human subtypes, only HPS-1 and HPS-4 develop pulmonary fibrosis in addition to the general clinical manifestations of oculocutaneous albinism and bleeding diathesis. We identified HPS-1 in three unrelated patients from different regions of India, who presented with iris transillumination, pale fundi, hypopigmentation, nystagmus, decreased visual acuity, and a bleeding diathesis. Two of these patients carried the homozygous mutation c.398+5G>A (IVS5+5G>A) in HPS1, resulting in skipping of exon 5 in HPS1 mRNA. The third patient carried a novel homozygous c.988−1G>T mutation that resulted in in-frame skipping of HPS1 exon 12 and removes 56 amino acids from the HPS1 protein. Given the discovery of HPS-1 in an ethnic group where oculocutaneous albinism (OCA) is highly prevalent, it is possible that HPS in India is under-diagnosed. We recommend that unconfirmed OCA patients in this ethic group be considered for mutational screening of known HPS genes, in particular c.398+5G>A and c.980−1G>T, to ensure that patients can be monitored and treated for clinical complications unique to HPS.