Journal Article

Germinal and Somatic Mutations in the <i>PKD2</i> Gene of Renal Cysts in Autosomal Dominant Polycystic Kidney Disease

Michael Koptides, Christos Hadjimichael, Panayiota Koupepidou, Alkis Pierides and C. Constantinou Deltas

in Human Molecular Genetics

Volume 8, issue 3, pages 509-513
Published in print March 1999 | ISSN: 0964-6906
Published online March 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.3.509
Germinal and Somatic Mutations in the PKD2 Gene of Renal Cysts in Autosomal Dominant Polycystic Kidney Disease

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Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in one of three genes: PKD1 on chromosome 16 accounts for ∼85% of cases whereas PKD2 on chromosome 4 accounts for ∼15%. Mutations in the PKD3 gene are rare. All patients present with similar clinical phenotypes, and the cardinal symptom is the formation of fluid-filled cysts in the kidneys. Previous work has provided data supporting the notion that cysts in ADPKD1 are focal in nature and form after loss of function of polycystin 1. This became evident by demonstrating that the normal PKD1 allele was inactivated somatically by loss of heterozygosity or by mutagenesis in a subset of renal or liver cysts examined. We show in this report, for the first time, multiple novel somatic mutations within the PKD2 gene of epithelial cells, in both kidneys of an ADPKD2 patient. From a total of 21 cysts examined, seven (33%) had the same C insertion within the inherited wild-type allele. In two other cysts, a nonsense mutation and a splice site AG deletion had occurred in a PKD2 allele that could not be identified as the inherited wild-type or mutant. We suggest that the autosomal dominant form of ADPKD2 occurs by a cellular recessive mechanism, supporting a two-hit model for cyst formation.

Journal Article.  3240 words.  Illustrated.

Subjects: Genetics and Genomics

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