Nature Genetics
14, 300 - 306 (1996)
doi:10.1038/ng1196-300
Positional cloning of a gene for Hermansky−Pudlak syndrome, a disorder of cytoplasmic organellesJangsuk Oh1, *, Tu Bailin1, *, Kazuyoshi Fukai1, *, Guo Hong Feng1, *, Lingling Ho1, Jen-i Mao2, Edgar Frenk3, Naoaki Tamura4
& Richard A. Spritz1, 5
1Departments of Medical Genetics and Pediatrics, University of Wisconsin, 445 Henry Mall, Madison, Wisconsin 53706, USA
2Collaborative Research Division, Genome Therapeutics Corp., Waltham, Massachusetts 02154, USA
3Service de dermatovenereologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
4Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan
*J.O., T.B., K.F. & G.H.F. contributed equally to this work
5e-mail: raspritz@facstaff.wisc.edu Hermansky−Pudlak syndrome (HPS) is an often−fatal autosomal recessive disease in which albinism, bleeding, and lysosomal storage result from defects of diverse cytoplasmic organelles: melanosomes, platelet dense bodies, and lysosomes. HPS is the most common single−gene disorder in Puerto Rico, with an incidence of 1 in 1,800. We have identified the HPS gene by positional cloning, and found homozygous frameshifts in this gene in Puerto Rican, Swiss, Irish and Japanese HPS patients. The HPS polypeptide is a novel transmembrane protein that is likely to be a component of multiple cytoplasmic organelles and that is apparently crucial for their normal development and function. The different clinical phenotypes associated with the different HPS frameshifts we observed suggests that differentially truncated HPS polypeptides may have somewhat different consequences for subcellular function.
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