Three 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 common in northwest Puerto Rico, where affected individuals are homozygous for a 16-bp duplication in the gene HPS. Two other homozygous frameshift mutations in HPS were previously identified among non-Puerto Rican 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 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 of HPS RNA by Northern blot analysis of fibroblasts, and all had significant pigment dilution. To date, all mutations in HPS result in a truncated protein, suggesting that the C-terminal portion of the HPS protein is functionally important.