title: Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome.
abstract: Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis. In a recent report on the cloning of an HPS gene, all 22 Puerto Rican HPS patients were homozygous for a 16-bp duplication in exon 15. This presumably reflected a founder effect for the HPS mutation in Puerto Rico. Nevertheless, we ascertained two individuals from central Puerto Rico who lacked the 16-bp duplication, exhibited significant amounts of normal-size HPS mRNA by northern blot analysis, and had haplotypes in the HPS region that were different from the haplotype of every 16-bp-duplication patient. Moreover, these two individuals displayed no mutations in their cDNA sequences, throughout the entire HPS gene. Both patients exhibited pigment dilution, impaired visual acuity, nystagmus, a bleeding diathesis, and absent platelet dense bodies, confirming the diagnosis of HPS. These findings indicate that analysis of Puerto Rican patients for the 16-bp duplication in HPS cannot exclude the diagnosis of HPS. In addition, HPS most likely displays locus heterogeneity, consistent with the existence of several mouse strains manifesting both pigment dilution and a platelet storage-pool deficiency.
authors.affiliation: Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1830, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hazelwood
authors.forename: V
authors.initials: V
authors.lastname: Shotelersuk
authors.forename: S C
authors.initials: SC
authors.lastname: Wildenberg
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: F
authors.initials: F
authors.lastname: Iwata
authors.forename: M I
authors.initials: MI
authors.lastname: Kaiser-Kupfer
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: R A
authors.initials: RA
authors.lastname: King
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D016115:Albinism, Oculocutaneous / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D001792:Blood Platelets / Q000648:ultrastructure; D015152:Blotting, Northern; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005260:Female; D018740:Genetic Heterogeneity; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010858:Pigmentation / Q000235:genetics; D010981:Platelet Storage Pool Deficiency / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011647:Puerto Rico; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D017931:DNA Primers