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Genetics and Pathogenesis of Autosomal Dominant Polycystic Kidney Disease: 20 Years On
Author(s) -
CornecLe Gall Emilie,
Audrézet MariePierre,
Le Meur Yannick,
Chen JianMin,
Férec Claude
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22708
Subject(s) - pkd1 , autosomal dominant polycystic kidney disease , biology , genetics , polycystic kidney disease , germline mutation , disease , phenotype , pathogenesis , genetic heterogeneity , allele , cystic kidney disease , kidney , mutation , gene , pathology , immunology , medicine
Autosomal dominant polycystic kidney disease ( ADPKD ), the most common inherited kidney disorder, is characterized by the progressive development and expansion of bilateral fluid‐filled cysts derived from the renal tubule epithelial cells. Although typically leading to end‐stage renal disease in late middle age, ADPKD represents a continuum, from neonates with hugely enlarged cystic kidneys to cases with adequate kidney function into old age. Since the identification of the first causative gene (i.e., PKD 1 , encoding polycystin 1) 20 years ago, genetic studies have uncovered a large part of the key factors that underlie the phenotype variability. Here, we provide a comprehensive review of these significant advances as well as those related to disease pathogenesis models, including mutation analysis of PKD 1 and PKD 2 (encoding polycystin 2), current mutation detection rate, allelic heterogeneity, genotype and phenotype relationships (in terms of three different inheritance patterns: classical autosomal dominant inheritance, complex inheritance, and somatic and germline mosaicism), modifier genes, the role of second somatic mutation hit in renal cystogenesis, and findings from mouse models of polycystic kidney disease. Based upon a combined consideration of the current knowledge, we attempted to propose a unifying framework for explaining the phenotype variability in ADPKD .