title: Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux.
abstract: 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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Elahi
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Homstad
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.|Duke Molecular Physiology Institute, Durham, NC, USA.
authors.forename: Himani
authors.initials: H
authors.lastname: Vaidya
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stout
authors.affiliation: Duke Molecular Physiology Institute, Durham, NC, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Gentzon
authors.initials: G
authors.lastname: Hall
authors.affiliation: Duke Molecular Physiology Institute, Durham, NC, USA.|Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Conlon
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.|Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Routh
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.|Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Wiener
authors.affiliation: Department of Surgery, Division of Urology, Duke University Medical Center, Durham, NC, USA.|Department of Urology, Pediatric Urology, UNC School of Medicine , University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Sherry S
authors.initials: SS
authors.lastname: Ross
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Nagaraj
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Delbert
authors.initials: D
authors.lastname: Wigfall
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: John
authors.initials: J
authors.lastname: Foreman
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892-5635, USA.
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.affiliation: Department of Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Indra R
authors.initials: IR
authors.lastname: Gupta
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Brophy
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: C Egla
authors.initials: CE
authors.lastname: Rabinovich
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. rasheed.gbadegesin@duke.edu.|Duke Molecular Physiology Institute, Durham, NC, USA. rasheed.gbadegesin@duke.edu.
authors.forename: Rasheed A
authors.initials: RA
authors.lastname: Gbadegesin
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007593:Joint Instability / Q000175:diagnosis; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D019063:Tenascin / Q000235:genetics*; D014718:Vesico-Ureteral Reflux / Q000235:genetics*
chemical_list: D019063:Tenascin
keywords: Joint hypermobility; Reflux nephropathy; Tenascin genes; Urinary tract infection; Vesicoureteral reflux