CIN '2007 - 4th CONGRESS OF NEPHROLOGY IN INTERNET
Molecular genetics of Polycystic Kidney Diseases
Dr Eliecer Coto García
Genética Molecular del Hospital Central de asturias, Oviedo
Abstract
Polycystic kidney diseases are a group of hereditary renal disorders with a familial dominant (Autosomal dominant polycystic kidney disease, ADPKD) or recessive (Autosomal recessive polycystic kidney disease, ARPKD) inheritance. Families with ADPKD have mutations in either PKD1 (chromosome 16) or PKD2 (chromosome 4) genes. PKD1 and PKD2 encode the polycystins,. ARPKD is the consequence of mutations in a single gene on chromosome 6, PKHD1, that encodes fibrocystin. Mutations in PKD1 have been associated with more severe forms compared to PKD2: significant younger age for End Stage Renal Disease (ESRD) and higher rates of morbi-mortality. In this way, ADPKD2 is considered a benign form compared to ADPKD1. Approximatelly, 90% of the ADPKD-families have mutations in PKD1. The polycystins-1 and 2 and the fibrocystin are expressed in the primary cilia of epithelial kidney cells, and the disfunction introduced by the mutated proteins is traduced in characteristic cellular phenotypic changes (compared to normal non-mutated cells): Renal cysts in epithelial cells, as a consequence of cellular de-diferenciation, with excessive fluid secretion, and proliferation; alteration of cellular pathways such as cilia, calcium homeostasis, cAMP, RAS/MAPK, and concentration capacity. Some drugs that target these pathways are under preclinical trials in humans: antiproliferative agents (such as targets of mTOR) and antagonists of vasopressin V2 receptors.Comments: