AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE - MOLECULAR ANALYSIS

Using a positional cloning approach the major autosomal dominant polyc ystic kidney disease (ADPKD) gene (PKD1) has been identified on chromo some 16: a disease associated chromosome translocation was instrumenta l in its identification. Study of the PKD1 gene has been complicated b ecause most of the gene lies in a genomic region reiterated elsewhere on the same chromosome. The duplicate area contains three genes which share substantial homology with PKD1 and generate polyadenylated trans cripts. Most PKD1 mutations have so far been detected in the single co py, 3' end of the gene, but a group of patients with deletion of PKD1 and the adjacent TSC2 gene, which have severe infantile polycystic kid ney disease, have also been characterised. The full length transcript of PKD1 (similar to 14 kb) has now been cloned and is predicted to enc ode a protein, polycystin, of 4302/3 aa. Polycystin contains multiple extracellular domains including leucine rich repeats, a C-type lectin, immunoglobulin and fibronectin type III-like domains and has a C term inal region which is likely associated with the membrane. These homolo gies indicate that polycystin is a cell-cell/ matrix interaction prote in.