Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans

Schönfelder, EM; Knüppel, T; Tasic, V; Miljkovic, P; Konrad, M; Wühl, E; Antignac, C; Bakkaloglu, A; Schaefer, F; Weber, S; ESCAPE, Trial Group (2006). Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans. American Journal of Kidney Diseases, 47(6), pp. 1004-12. Philadelphia, Pa.: W.B. Saunders 10.1053/j.ajkd.2006.02.177

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BACKGROUND: Renal hypodysplasia, characterized by a decrease in nephron number, small overall kidney size, and maldeveloped renal tissue, is a leading cause of chronic renal failure in young children. Familial clustering and renal hypodysplasia phenotypes observed in transgenic animal models suggest a genetic contribution. Uroplakin IIIa (encoded by UPIIIA) is an integral membrane protein present in urothelial plaques, and the murine UPIIIa knockout is associated with urothelial anomalies and vesicoureteral reflux. De novo UPIIIA mutations recently were identified in 4 of 17 patients with severe bilateral renal adysplasia. METHODS: To evaluate the overall role of UPIIIA in human renal hypodysplasia pathogenesis, we performed UPIIIA mutation analysis in a cohort of 170 pediatric patients affected by severe unilateral or bilateral renal hypodysplasia. Eighty-one patients were affected by bilateral nonobstructive renal hypodysplasia; of these, 61 were without vesicoureteral reflux. Eighty-four patients presented with unilateral nonobstructive renal hypodysplasia, including 24 patients with unilateral multicystic dysplastic kidneys. Family history was positive in 11%. RESULTS: Mutation analysis showed 2 heterozygous mutations not observed in 200 race-matched control chromosomes. In only 1 family was distribution of the UPIIIA mutation consistent with a disease-causing effect. This de novo missense mutation (Gly202Asp) was identified in a patient with unilateral multicystic dysplastic kidneys. The second (intronically located) mutation appeared unlikely to be disease causing because it did not segregate with an obvious disease phenotype in the affected family. CONCLUSION: Our results indicate that de novo mutations in UPIIIA can be involved in defective early kidney development, but probably constitute only a rare cause of human renal hypodysplasia in a minor subset of individuals.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
UniBE Contributor:	Konrad, Martin
ISSN:	0272-6386
ISBN:	16731295
Publisher:	W.B. Saunders
Language:	English
Submitter:	Anette van Dorland
Date Deposited:	04 Oct 2013 14:50
Last Modified:	05 Dec 2022 14:15
Publisher DOI:	10.1053/j.ajkd.2006.02.177
PubMed ID:	16731295
Web of Science ID:	000238390400008
URI:	https://boris.unibe.ch/id/eprint/20926 (FactScience: 4724)