Clinical, Molecular, and Cellular Features of Non-Puerto Rican Hermansky–Pudlak Syndrome Patients of Hispanic Descent

Abstract

Hermansky-Pudlak syndrome is an autosomal recessive condition characterized by a bleeding diathesis and hypopigmentation of the skin, hair and eyes. Some HPS patients develop other complications such as granulomatous colitis and/or a fatal pulmonary fibrosis. Eight genes have been associated with the condition, resulting in subtypes HPS-1 through HPS-8. The HPS gene products are involved in the biogenesis of specialized lysosome-related organelles such as melanosomes, platelet delta granules and others. HPS1 and HPS4 form a stable complex named BLOC-3, and patients with BLOC-3 or AP-3 deficiency develop pulmonary fibrosis. Therefore, it is important to subtype each HPS patient. HPS type 1 (HPS-1) occurs frequently on the island Puerto Rico due to a founder mutation. Here, we describe seven mutations, six of which are previously unreported, in the HPS1, HPS4 and HPS5 genes among patients of Mexican, Uruguayan, Honduran, Cuban, Venezuelan and Salvadoran ancestries. Our findings demonstrate that the diagnosis of HPS should be considered in Hispanic patients with oculocutaneous albinism and bleeding symptoms. Moreover, such patients should not be assumed to have the HPS-1 subtype typical of northwest Puerto Rican patients. We recommend molecular HPS subtyping in such cases, since it may have significant implications for prognosis and intervention.