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Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth

Terry Watnick, MD
William M Bennett, MD
Section Editors
Ronald D Perrone, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Alice M Sheridan, MD


Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder, occurring in approximately 1 in every 400 to 1000 live births [1,2]. It is estimated that less than one-half of affected individuals will be diagnosed during their lifetime since the disease is often clinically silent [1].

The genetics of ADPKD and the mechanisms of cyst growth will be reviewed here. Issues related to the diagnosis of and screening for ADPKD and for autosomal recessive polycystic kidney disease, which is a disease of children, are discussed separately. (See "Diagnosis of and screening for autosomal dominant polycystic kidney disease" and "Autosomal recessive polycystic kidney disease in children".)


Mutations in one of two genes, PKD1 or PKD2, account for most cases of ADPKD. The two disease loci segregate independently since they reside on separate chromosomes. The PKD1 gene is located on chromosome 16p13.3, and the PKD2 gene is located on chromosome 4q21. (See 'PKD1 and PKD2 genes' below.)

There is evidence that the PKD1 and PKD2 disease loci can have synergistic effects. A family has been reported with bilineal inheritance, in which one parent had a mutation in PKD1 and the other parent had a mutation in PKD2 [3]. The two family members with both mutations progressed to end-stage renal disease (ESRD) approximately 20 years earlier than family members with only one PKD1 or PKD2 mutation.

A few families with ADPKD are not linked to either locus [4-6]. However, a third ADPKD gene has not been identified. A study that re-evaluated five such families has shown that the absence of linkage was due to misdiagnosis, DNA contamination, and genotype errors and did not support the presence of a third gene [7].


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Literature review current through: Sep 2016. | This topic last updated: Feb 25, 2016.
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