Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2. The products of these genes associate to form heteromeric complexes. Several models have been proposed to explain the mechanism of cyst formation. Here we find somatic mutations of PKD2 in 71% of ADPKD2 cysts analysed. Clonal somatic mutations of PKD1 were identified in a subset of cysts that lacked PKD2 mutations.

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Figure 1: Somatic mutations of PKD1 in PKD2 cysts.

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Acknowledgements

We thank the individuals with ADPKD and their families for participation. This work was supported by the NIH (DK48006, DK02562), the Polycystic Kidney Disease Research Foundation and the Kidney Foundation of Canada. G.G.G. is the Irving Blum Scholar of the Johns Hopkins University School of Medicine.

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Correspondence to Gregory Germino or York Pei.

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