Novel mutations in the HPS1 gene among Puerto Rican patients

• Published in: Clinical genetics 2011-06, Vol.79 (6), p.561-567
• Main Authors: Carmona-Rivera, C, Hess, RA, O'Brien, K, Golas, G, Tsilou, E, White, JG, Gahl, WA, Huizing, M
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Adult; Albinism; Alternative Splicing; Amino acid sequence; Base Sequence; bleeding diathesis; BLOC-3; DNA Mutational Analysis; Evolution; Exons; Female; Genetic disorders; Hermanski-Pudlak Syndrome - diagnosis; Hermanski-Pudlak Syndrome - genetics; Hermansky-Pudlak syndrome; Hispanic people; Humans; Islands; Male; Membrane Proteins - genetics; Missense mutation; Molecular Sequence Data; mRNA; Mutation; Mutation, Missense; Nonsense mutation; Organelles; platelet dense body; Platelets; Population genetics; Puerto Rico; pulmonary fibrosis; Splice junctions; Stop codon; Young Adult
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01491.x

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.H497QfsX90). 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.M325WfsX6). 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.