The Transmission of Vesicoureteral Reflux from Parent to Child

Noe, H. Norman; Wyatt, Robert; Peeden, Joseph N.; Rivas, Marian L.

doi:10.1016/s0022-5347(17)37053-2

Cited by 149 publications

(65 citation statements)

References 18 publications

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“…VUR presents in association with other urogenital anomalies such as renal aplasia, multicystic dysplastic kidney, duplicated ureters, or ureteropelvic junction (UPJ) obstruction (6,7), suggesting a common pathogenic link between these disorders. In addition, increased sibling recurrence rates (30% to 50%) as well as parent-offspring transmission strongly implicate hereditary factors in the development of VUR (8,9). The severity of VUR varies between affected individuals in a family, and the abnormalities often improve or can entirely resolve with age, making complete ascertainment of affected family members difficult.…”

Section: P Rimary Vesicoureteral Reflux (Vur) (Online Mendelianmentioning

confidence: 99%

Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds

Sanna‐Cherchi¹,

Reese²,

Hensle³

et al. 2005

Journal of the American Society of Nephrology

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Vesicoureteral reflux (VUR) (OMIM %193000), a common cause of childhood renal failure, is strongly influenced by hereditary factors. Familial VUR most closely conforms to autosomal-dominant inheritance, but because of variable penetrance and expressivity, large multigenerational pedigrees tractable to linkage analysis have been difficult to ascertain. A single genome-wide study of familial VUR has demonstrated linkage to chromosome 1p13, with 78% locus heterogeneity. Previous studies in humans have also suggested loci on chromosomes 6p21, 10q26, and 19q13, whereas mutations in ROBO2 were recently reported in some patients with VUR. Replication of these studies was attempted in seven previously undescribed families from Italy and the United States. Simulation studies, assuming 50% locus heterogeneity, showed that these kindreds had 85% power to replicate linkage and 53% power to achieve genome-wide significance at candidate intervals. Thirty-five markers on chromosomes 1p13, 3p12, 6p21, 10q26, and 19q13 were genotyped and analysis of linkage under a variety of models was performed. Parametric analysis excluded linkage to all candidate loci under genetic homogeneity; moreover, the data did not support statistically significant linkage under models of locus heterogeneity. Similarly, nonparametric, allele-sharing analysis did not reveal any evidence of linkage at any of the loci tested. Thus, despite sufficient power, linkage of familial VUR to previously reported candidate intervals could not be replicated. These data demonstrate substantial genetic heterogeneity of VUR and suggest that mapping strategies relying on a large number of kindreds or single "loaded" pedigrees will be most effective to achieve replication or detection of linkage.

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Section: P Rimary Vesicoureteral Reflux (Vur) (Online Mendelianmentioning

confidence: 99%

Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds

Sanna‐Cherchi¹,

Reese²,

Hensle³

et al. 2005

Journal of the American Society of Nephrology

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“…1 Over the past 30 years, clinical observations have suggested a genetic basis for VUR. 2 There is a 30-50% incidence of VUR in first-degree relatives of probands, 3,4 a 100% concordance of VUR among monozygotic twins and 50% among dizygotic twins. 5 Genetic linkage to loci on chromosomes 1, 6, 10 and 13 has been previously observed.…”

Section: Introductionmentioning

confidence: 99%

A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5

et al. 2009

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The basis for vesicoureteral reflux (VUR) is considered to be primarily genetic, with a 30-50% incidence of VUR in first-degree relatives of patients. The search for the causative gene or genes has been elusive, likely because of VUR being genetically heterogeneous with complex inheritance patterns. In this study, a genome-wide analysis of VUR with high-density single nucleotide polymorphisms was conducted with the aim of identifying susceptibility loci for VUR in 98 families with two or more affected children. Using the affected sib-pair method of analysis in 150 sib-pairs, we identified a genome-wide statistically significant linkage peak with an LOD score greater than 4 on chromosome 5 and two linkage peaks with LOD scores greater than 3.6 on chromosomes 13 and 18 were identified in these 98 families. These results suggested that multiple genes are likely to contribute to the formation of VUR phenotype. Further mapping of these linkage peaks may help identify the causative genes.

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“…9 -12 Sibling recurrence rates of 30% to 65% have suggested segregation of a single gene or oligogenes with large effects. 9,[12][13][14] Interestingly however, the three published genome-wide linkage scans of pVUR have strongly suggested multifactorial determination. [15][16][17] Two pVUR loci have been identified with genome-wide significance on chromosomes 1p13 and 2q37 under an autosomal dominant transmission with locus heterogeneity.…”

mentioning

confidence: 99%

A Recessive Gene for Primary Vesicoureteral Reflux Maps to Chromosome 12p11-q13

Weng

Sanna‐Cherchi

Hensle

et al. 2009

Journal of the American Society of Nephrology

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Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR. We performed a genome-wide linkage scan in 12 large families segregating pVUR, comprising 72 affected individuals. To avoid potential misspecification of the trait locus, we performed a parametric linkage analysis using both dominant and recessive models. Analysis under the dominant model yielded no signals across the entire genome. In contrast, we identified a unique linkage peak under the recessive model on chromosome 12p11-q13 (D12S1048), which we confirmed by fine mapping. This interval achieved a peak heterogeneity LOD score of 3.6 with 60% of families linked. This heterogeneity LOD score improved to 4.5 with exclusion of two high-density pedigrees that failed to link across the entire genome. The linkage signal on chromosome 12p11-q13 originated from pedigrees of varying ethnicity, suggesting that recessive inheritance of a high frequency risk allele occurs in pVUR kindreds from many different populations. In conclusion, this study identifies a major new locus for pVUR and suggests that in addition to genetic heterogeneity, recessive contributions should be considered in all pVUR genome scans.

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The Transmission of Vesicoureteral Reflux from Parent to Child

Cited by 149 publications

References 18 publications

Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds

Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds

A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5

A Recessive Gene for Primary Vesicoureteral Reflux Maps to Chromosome 12p11-q13

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