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Novel mutations in the HPS1 gene among Puerto Rican patients
Author(s) -
CarmonaRivera C,
Hess RA,
O'Brien K,
Golas G,
Tsilou E,
White JG,
Gahl WA,
Huizing M
Publication year - 2011
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01491.x
Subject(s) - frameshift mutation , oculocutaneous albinism , exon , genetics , missense mutation , biology , gene duplication , splice site mutation , compound heterozygosity , mutation , hermansky–pudlak syndrome , gene , medicine , alternative splicing , pulmonary fibrosis , fibrosis
Carmona‐Rivera C, Hess RA, O’Brien K, Golas G, Tsilou E, White JG, Gahl WA, Huizing M. Novel mutations in the HPS1 gene among Puerto Rican patients. Hermansky‐Pudlak syndrome (HPS) is a disorder of oculocutaneous albinism (OCA) and platelet storage pool deficiency. Eight different disease‐causing genes have been identified, whose gene products are thought to be involved in the biogenesis of lysosome‐related organelles. HPS type 1 (HPS‐1) is the most common HPS subtype in Puerto Rico, with a frequency of 1:1800 in the northwest of the island due to a founder mutation, i.e. a 16‐bp duplication in exon 15 of the HPS1 gene (c.1472_1487dup16; p.H497Q fs X90). We identified three Puerto Rican HPS‐1 patients who carried compound heterozygous HPS1 mutations. One patient was heterozygous for c.937G>A, causing a missense mutation (p.G313S) at the 3′ splice junction of exon 10. This mutation resulted in activation of a cryptic intronic splice site causing an aberrantly spliced HPS1 mRNA that included 144‐bp of intronic sequence, producing 11 novel amino acids followed by a stop codon. The other two patients were heterozygous for the previously reported c.972delC in HPS1 , resulting in a frameshift and a premature stop codon (p.M325W fs X6). These findings indicate that, among Puerto Ricans, other HPS1 mutations apart from the 16‐bp duplication should be considered in the analysis of this population.