THE POLYCYSTIC KIDNEY-DISEASE-1 GENE ENCODES A 14-KB TRANSCRIPT AND LIES WITHIN A DUPLICATED REGION ON CHROMOSOME-16

Autosomal dominant polycystic kidney disease (ADPKD) is a common genet ic disorder that frequently results in renal failure due to progressiv e cyst development. The major locus, PKD1, maps to 16p13.3. We identif ied a chromosome translocation associated with APPKD that disrupts a g ene (PBP) encoding a 14 kb transcript in the PKD1 candidate region. Fu rther mutations of the PBP gene were found in PKD1 patients, two delet ions (one a de novo event) and a splicing defect, confirming that PBP is the PKD1 gene. This gene is located adjacent to the TSC2 locus in a genomic region that is reiterated more proximally on 16p. The duplica te area encodes three transcripts substantially homologous to the PKD1 transcript. Partial sequence analysis of the PKD1 transcript shows th at it encodes a novel protein whose function is at present unknown.