Mutations in Uroplakin IIIA Are a Rare Cause of Renal Hypodysplasia in Humans
| Autor: | Tanja Knüppel, Franz Schaefer, Stefanie Weber, Aysin Bakkaloglu, Martin Konrad, Elke Wühl, Corinne Antignac, Velibor Tasic, Predrag Miljkovic, Eva-Maria Schönfelder |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Nephrology medicine.medical_specialty Pathology Adolescent Urinary system Molecular Sequence Data Mutation Missense Kidney development Nephron Kidney Vesicoureteral reflux Cohort Studies Internal medicine medicine Humans Missense mutation Multicystic Dysplastic Kidney Amino Acid Sequence Child Ultrasonography Uroplakin III Membrane Glycoproteins business.industry medicine.disease Pedigree medicine.anatomical_structure Dysplasia Child Preschool Urogenital Abnormalities Kidney Failure Chronic Female business |
| Zdroj: | American Journal of Kidney Diseases. 47:1004-1012 |
| ISSN: | 0272-6386 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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