Genetic Mutations in Autosomal Dominant Polycystic Kidney Disease Type-1

Polycystic kidney disease (PKD) is mainly characterized by formation of cysts in kidney with associated kidney malfunction. The cysts eventually grow larger leading to end stage renal failure (ESRF) requiring kidney dialysis or transplant. There are various genetic forms of PKD: autosomal dominant type 1 (ADPKD1), type 2 (ADPKD2) and even a third type (ADPKD3) is known to exist. There is also a recessive form of PKD (ARPKD). The autosomal dominant type is caused due a single defective dominant gene in a single chromosome of the homologous pair among the autosomes and the recessive type is caused due to defect in both genes of a homologous pair. Each of these PKD types adversely impact structure and function of their associated protein products. For instance, ADPKD1 impacts polycystin-1, ADPKD2 impacts polycystin-2, and ARPKD impacts fibrocystin. There are several known mutations for each of these PKD disease types, e.g., there are over 250 known mutations of ADPKD1 gene. In this paper we restrict ourselves to ADPKD1 and a specific mutation (L845S) to demonstrate how a genetic mutation leads to malfunction of PKD1 gene.