Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux.

Journal Article (Journal Article)

BACKGROUND: Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract, and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in the tenascin XB gene (TNXB) as a cause of PVUR with joint hypermobility. METHODS: To define the role of rare variants in tenascin genes in the etiology of PVUR, we screened a cohort of patients with familial PVUR (FPVUR) and non-familial PVUR (NFPVUR) for rare missense variants inTNXB and the tenascin C gene (TNC) after excluding mutations in ROBO2 and SOX17. RESULTS: The screening procedure identified 134 individuals from 112 families with PVUR; two families with mutations in ROBO2 were excluded from further analysis. Rare missense variants in TNXB were found in the remaining 110 families, of which 5/55 (9%) families had FPVUR and 2/55 (4%) had NFPVUR. There were no differences in high-grade reflux or renal parenchymal scarring between patients with and without TNXB variants. All patients with TNXB rare variants who were tested exhibited joint hypermobility. Overall we were able to identify causes of FPVUR in 7/57 (12%) families (9% in TNXB and 3% in ROBO2). CONCLUSIONS: In conclusion, the identification of a rare missense variant in TNXB in combination with a positive family history of VUR and joint hypermobility may represent a non-invasive method to diagnose PVUR and warrants further evaluation in other cohorts.

Full Text

Duke Authors

Cited Authors

  • Elahi, S; Homstad, A; Vaidya, H; Stout, J; Hall, G; Wu, G; Conlon, P; Routh, JC; Wiener, JS; Ross, SS; Nagaraj, S; Wigfall, D; Foreman, J; Adeyemo, A; Gupta, IR; Brophy, PD; Rabinovich, CE; Gbadegesin, RA

Published Date

  • February 2016

Published In

Volume / Issue

  • 31 / 2

Start / End Page

  • 247 - 253

PubMed ID

  • 26408188

Pubmed Central ID

  • PMC4747108

Electronic International Standard Serial Number (EISSN)

  • 1432-198X

Digital Object Identifier (DOI)

  • 10.1007/s00467-015-3203-6


  • eng

Conference Location

  • Germany