ORGANIZATION AND NUCLEOTIDE-SEQUENCE OF THE HUMAN HERMANSKY-PUDLAK SYNDROME (HPS) GENE

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder cha racterized by oculocutaneous albinism, bleeding tendency, and lysosoma l ceroid storage disease, associated with defects of multiple cytoplas mic organelles-melanosomes, platelet-dense granules, and lysosomes. HP S is frequently fatal and is the most common single-gene disorder in P uerto Rico. We previously characterized the human HPS cDNA and identif ied pathologic mutations in the gene in patients with HPS. The HPS pro tein is a novel apparent transmembrane polypeptide that seems to be cr ucial for normal organellar development, Here we describe the structur al organization, nucleotide sequence, and polymorphisms of the human H PS gene, The gene consists of 20 exons spanning about 30.5 kb in chrom osome segment 10q23.1-q23.3. One of the intervening sequences is a mem ber of the novel, very rape class of so-called ''AT-AC'' introns, defi ned by highly atypical 5' and 3' splice site and branch site consensus sequences that provide novel targets for possible pathologic gene mut ations, This information provides the basis for molecular analyses of patients with HPS and will greatly facilitate diagnosis and carrier de tection of this severe disorder.