Human Molecular Genetics, Vol 8, 509-513, Copyright © 1999 by Oxford University Press
M Koptides, C Hadjimichael, P Koupepidou, A Pierides and C Constantinou Deltas
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations
in one of three genes: PKD1 on chromosome 16 accounts for approximately 85%
of cases whereas PKD2 on chromosome 4 accounts for approximately 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.
ARTICLES
Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease
The Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Nicosia General Hospital, Nicosia, Cyprus.
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