title: Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.
abstract: Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles-melanosomes, platelet-dense granules, and lysosomes. As reported elsewhere, we mapped the human HPS gene to chromosome segment 10q23, positionally cloned the gene, and identified three pathologic mutations of the gene, in patients from Puerto Rico, Japan, and Europe. Here, we describe mutation analysis of 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication, the result of an apparent founder effect, is nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. We also describe six novel HPS mutations: a 5' splice-junction mutation of IVS5, three frameshifts, a nonsense mutation, and a one-codon in-frame deletion. These mutations define an apparent frameshift hot spot at codons 321-322. Overall, however, we detected mutations in the HPS gene in only about half of non-Puerto Rican patients, and we present evidence that suggests locus heterogeneity for HPS.
authors.affiliation: Department of Medical Genetics, University of Wisconsin, Madison 53706, USA.
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: L
authors.initials: L
authors.lastname: Ho
authors.forename: S
authors.initials: S
authors.lastname: Ala-Mello
authors.forename: D
authors.initials: D
authors.lastname: Amato
authors.forename: L
authors.initials: L
authors.lastname: Armstrong
authors.forename: S
authors.initials: S
authors.lastname: Bellucci
authors.forename: G
authors.initials: G
authors.lastname: Carakushansky
authors.forename: J P
authors.initials: JP
authors.lastname: Ellis
authors.forename: C T
authors.initials: CT
authors.lastname: Fong
authors.forename: J S
authors.initials: JS
authors.lastname: Green
authors.forename: E
authors.initials: E
authors.lastname: Heon
authors.forename: E
authors.initials: E
authors.lastname: Legius
authors.forename: A V
authors.initials: AV
authors.lastname: Levin
authors.forename: H K
authors.initials: HK
authors.lastname: Nieuwenhuis
authors.forename: A
authors.initials: A
authors.lastname: Pinckers
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: M L
authors.initials: ML
authors.lastname: Whiteford
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: R A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003241:Consanguinity; D005006:Ethnicity / Q000235:genetics; D016368:Frameshift Mutation; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D011647:Puerto Rico / Q000208:ethnology; D012326:RNA Splicing