title: Clinical, molecular, and cellular features of non-Puerto Rican Hermansky-Pudlak syndrome patients of Hispanic descent.
abstract: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive condition characterized by a bleeding diathesis and hypopigmentation of the skin, hair, and eyes. Some HPS patients develop other complications such as granulomatous colitis and/or fatal pulmonary fibrosis. Eight genes have been associated with this condition, resulting in subtypes HPS-1 through HPS-8. The HPS gene products are involved in the biogenesis of specialized lysosome-related organelles such as melanosomes and platelet delta granules. HPS1 and HPS4 form a stable complex named biogenesis of lysosome-related organelles complex (BLOC)-3, and patients with BLOC-3 or AP-3 deficiency develop pulmonary fibrosis. Therefore, it is important to subtype each HPS patient. HPS type 1 (HPS-1) occurs frequently on the island of Puerto Rico because of a founder mutation. Here, we describe seven mutations, six of which, to our knowledge, are previously unreported in the HPS1, HPS4, and HPS5 genes among patients of Mexican, Uruguayan, Honduran, Cuban, Venezuelan, and Salvadoran ancestries. Our findings demonstrate that the diagnosis of HPS should be considered in Hispanic patients with oculocutaneous albinism and bleeding symptoms. Moreover, such patients should not be assumed to have the HPS-1 subtype typical of northwest Puerto Rican patients. We recommend molecular HPS subtyping in such cases, as it may have significant implications for prognosis and intervention.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1851, USA. carmelo.carmona@upr.edu
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carmona-Rivera
authors.forename: Gretchen
authors.initials: G
authors.lastname: Golas
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hess
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Cardillo
authors.forename: Elijah H
authors.initials: EH
authors.lastname: Martin
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Tsilou
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.forename: James G
authors.initials: JG
authors.lastname: White
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D020662:Guanine Nucleotide Exchange Factors; D006470:Hemorrhage / Q000235:genetics; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D011506:Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; C102160:HPS1 protein, human; C451752:HPS4 protein, human; C493900:HPS5 protein, human; D008565:Membrane Proteins; D011506:Proteins