Evidence for locus heterogeneity in Puerto Ricans with Hermansky-Pudlak syndrome.
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.
Hazelwood
S
S
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.
Shotelersuk
V
V
Wildenberg
S C
SC
Chen
D
D
Iwata
F
F
Kaiser-Kupfer
M I
MI
White
J G
JG
King
R A
RA
Gahl
W A
WA
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
D017931:DNA Primers