IDENTIFICATION OF THE RESPONSIBLE GENE FOR MEDULLARY CYSTIC KIDNEY DISEASE IN SEVEN EXTENDED PEDIGREES COLLECTED WITHIN THE ITALIAN COLLABORATIVE WORKING GROUP

Medullary cystic kidney disease (MCKD) is an interstitial nephropathy with dominant inheritance (AD). It occurs in adults with chronic renal failure which leads to rapid deterioration of renal functions. ADMCKD is a pathology that shows a clear genetic heterogeneity. Causes are yet unknown as the gene or genes involved in this pathology have not been identified yet. Various families have been studied through linkage analysis leading to the identification of at least 2 loci mapping on two distinct chromosomes, one on 1q21 and the other one on 16p12. The last one was described by our group. This discovery encouraged new molecular analysis on genes mapped on that region and involved in some renal function. Candidate genes with a higher possibility of being involved in the genesis of the disease, UMOD, SAH, gENAC, BK, KS and others, had already been examined in 7 families investigated, with no relevant results. The main object of our project is to identify the gene responsible for ADMCKD2. This could be reached both detecting other candidate genes in the region considered and examining the sequences of the tracts limited by linkage analysis in order to find new genes not detected yet. In case of genes supposed to be involved in the genesis of the disease, we intend to see whether those affected by the disease within the families examined share some characteristics with such genes that make them distinguishable from those not sick. This research could bring very important results. It would not only widen our knowledge on the pathogenesis of this disease but also help us to detect the patients with a higher risk of being affected by the disease or still to develop new therapeutic strategies.