title: Novel mutations in the HPS1 gene among Puerto Rican patients.
abstract: 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.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. carmonac@mail.nih.gov
authors.forename: C
authors.initials: C
authors.lastname: Carmona-Rivera
authors.forename: R A
authors.initials: RA
authors.lastname: Hess
authors.forename: K
authors.initials: K
authors.lastname: O'Brien
authors.forename: G
authors.initials: G
authors.lastname: Golas
authors.forename: E
authors.initials: E
authors.lastname: Tsilou
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
authors.forename: M
authors.initials: M
authors.lastname: Huizing
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011647:Puerto Rico; D055815:Young Adult
chemical_list: C102160:HPS1 protein, human; D008565:Membrane Proteins