3 NEW MUTATIONS IN A GENE CAUSING HERMANSKY-PUDLAK-SYNDROME - CLINICAL CORRELATIONS

Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. HPS is c ommon in northwest Puerto Rico, where affected individuals are homozyg ous for a 16-bp duplication in the gene HPS. Two other homozygous fram eshift mutations in HPS were previously identified among non-Puerto Ri can patients, Eighteen non-Puerto Rican HPS families were studied and HPS mutations 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 exhibit ed compound heterozygosity for these mutations, although most previous ly reported HPS patients have been homozygous for a particular mutatio n. All the newly described mutations were associated with decreased or undetectable levels of HPS RNA by Northern blot analysis of fibroblas ts, and all had significant pigment dilution, To date, all mutations i n HPS result in a truncated protein, suggesting that the C-terminal po rtion of the HPS protein is functionally important. (C) 1998 Academic Press.