Primary, Nonsyndromic Vesicoureteric Reflux and Its Nephropathy Is Genetically Heterogeneous, with a Locus on Chromosome 1

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• 作者：Sally A. Feather ; Sue Malcolm ; Adrian S. Woolf ; Victoria Wright ; Diana Blaydon ; Christopher J.D. Reid ; Frances A. Flinter ; Willem Proesmans ; Koen Devriendt ; Joan Carter ; Paul Warwicker ; Timothy H.J. Goodship ; Judith A. Goodship
• 刊名：The American Journal of Human Genetics
• 出版年：2000
• 出版时间：April 2000
• 年：2000
• 卷：66
• 期：4
• 页码：1420-1425
• 全文大小：646 K

文摘

Primary vesicoureteric reflux (VUR) affects 1 % –2 % of whites, and reflux nephropathy (RN) causes up to 15 % of end-stage renal failure in children and adults. There is a 30–50-fold increased incidence of VUR in first-degree relatives of probands, compared with the general population. We report the results of the first genomewide search of VUR and RN; we studied seven European families whose members exhibit apparently dominant inheritance. We initially typed 387 polymorphic markers spaced, on average, at 10 cM throughout the genome; we used the GENEHUNTER program to provide parametric and nonparametric linkage analyses of affected individuals. The most positive locus spanned 20 cM on 1p13 between GATA176C01 and D1S1653 and had a nonparametric LOD score (NPL) of 5.76 (P=.0002) and a parametric LOD score of 3.16. Saturation with markers at 1-cM intervals increased the NPL to 5.94 (P=.00009). Hence, VUR maps to a locus on chromosome 1. There was evidence of genetic heterogeneity at the chromosome 1 locus, and 12 additional loci were identified genomewide, with P<.05. No significant linkage was found to 6p, where a renal and ureteric malformation locus has been reported, or to PAX2, mutations of which cause VUR in renal-coloboma syndrome. Our results support the hypothesis that VUR is a genetic disorder.