Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease
| Autor: | Koptides, Michael, Hadjimichael, C., Koupepidou, P., Pierides, Alkis M., Constantinou-Deltas, Constantinos D. |
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| Přispěvatelé: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| Rok vydání: | 1999 |
| Předmět: |
TRPP Cation Channels
nonsense mutation Loss of Heterozygosity urologic and male genital diseases autosomal dominant disorder male kidney epithelium Humans case report controlled study somatic mutation human gene mutation Polymorphism Single-Stranded Conformational Germ-Line Mutation Aged Base Sequence urogenital system human cell article Membrane Proteins DNA Polycystic Kidney Autosomal Dominant female genital diseases and pregnancy complications Pedigree kidney polycystic disease priority journal Mutation polycystin Female germ line |
| Zdroj: | Human molecular genetics Hum.Mol.Genet. |
| Popis: | 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 ADPKDS 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. 8 509 513 Cited By :70 |
| Databáze: | OpenAIRE |
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