IDENTIFICATION OF A NOVEL TRANSCRIPT PRODUCED BY THE GENE RESPONSIBLEFOR THE HERMANSKY-PUDLAK-SYNDROME IN PUERTO-RICO

Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive disorde r that is characterized by oculocutaneous albinism, a predisposition t o mild bleeding caused by storage-pool deficient platelets, and a cero id storage disorder. A gene responsible for HPS in Puerto Rico maps to chromosome 10q2 and isolation of the gene has been reported, We have now identified a variant HPS cDNA that contains the same 5' sequence a s the published HPS gene and a unique 3' sequence. Analysis of genomic DNA suggests that the two cDNA are derived from alternative transcrip ts of a single gene; two polyadenylated transcripts were found in norm al human melanocytes, human bone marrow cells, human melanoma cells, l ymphoblastoid cell lines, and megakaryocytic leukemia cells by reverse transcriptase polymerase chain reaction and northern analysis. The sp licing exhibited by this gene is identical to the splicing found to pr oduce two alternative transcripts of the Chediak-Higashi Syndrome gene , another pigment disorder exhibiting platelet storage pool deficiency . These studies show that the HPS gene on chromosome 10 is complex and may have more than one biologically active transcript.