Three New Mutations in a Gene Causing Hermansky–Pudlak Syndrome: Clinical Correlations

Abstract

Hermansky–Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. HPS is common in northwest Puerto Rico, where affected individuals are homozygous for a 16-bp duplication in the geneHPS.Two other homozygous frameshift mutations inHPSwere previously identified among non-Puerto Rican patients. Eighteen non-Puerto Rican HPS families were studied andHPSmutations in three of them identified. One mutation, T322insC, has been previously described. However, three additional mutations, E133X, T322delC, and S396delC, have not been reported. Two families exhibited compound heterozygosity for these mutations, although most previously reported HPS patients have been homozygous for a particular mutation. All the newly described mutations were associated with decreased or undetectable levels ofHPSRNA by Northern blot analysis of fibroblasts, and all had significant pigment dilution. To date, all mutations inHPSresult in a truncated protein, suggesting that the C-terminal portion of the HPS protein is functionally important.