Characterization of the Hermansky-Pudlak Syndrome in the Puerto Rican population

Abstract

Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder consisting of a triad of tyrosinase-positive albinism, an accumulation of ceroid in tissues and a bleeding tendency due to storage pool deficient platelets. HPS is frequently found in the Puerto Rican population and a village of the Swiss Alps. Dense bodies analysis is considered the best way to diagnose this condition, because the majority of the HPS patients have a disminished number of granules on platelets, if they are not completely absent. In 1996 HPS gene was identified by linkage disequilibrium mapping and positional cloning. A 16 bp duplication leads to a frameshift mutation on exon 15 in the Puerto Rican patients. Frameshift mutations have also been found in Swiss, Irish and Japanese HPS patients. We have screened a total of 63 Puerto Rican patients for the 16 bp duplication and identified 30 (47.6%) positive homozygotes, 29 (46.0%) negative homozygotes and 4 (6.3%) heterozygotes. Based on the molecular and clinical data, we selected 8 duplication-negative patients whose bleeding times were higher than 15 minutes to perform exon. screening looking for other mutations in the HPS gene. We also gathered additional clinical data available and patient family history. None of these patients had mutations in the HPS gene when they were screened by non radioactive SSCP and DNA sequencing. Electron Microscope analysis of platelets from some of the duplication-negative patients revealed a wide spectrum of dense bodies abundancies ranging between 2 to 8 dense bodies. We are currently screening these patients to find a second HPS gene in the Puerto Rican population. We acknowledge support from NIH RCMI-G12 RR 0305, NIH-RO1-AR-39892, and UPR School of Medicine.