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Pediatric Nephrology

, Volume 31, Issue 2, pp 247–253 | Cite as

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

  • Shan Elahi
  • Alison Homstad
  • Himani Vaidya
  • Jennifer Stout
  • Gentzon Hall
  • Guanghong Wu
  • Peter ConlonJr
  • Jonathan C. Routh
  • John S. Wiener
  • Sherry S. Ross
  • Shashi Nagaraj
  • Delbert Wigfall
  • John Foreman
  • Adebowale Adeyemo
  • Indra R. Gupta
  • Patrick D. Brophy
  • C. Egla Rabinovich
  • Rasheed A. Gbadegesin
Original Article

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.

Keywords

Vesicoureteral reflux Tenascin genes Joint hypermobility Urinary tract infection Reflux nephropathy 

Notes

Acknowledgments

This study was supported by the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R21DK096200 and the Bayden Collins Pediatric Kidney Disease Research Fund, Duke University Medical Center. RG is the recipient of the Doris Duke Clinical Research Mentorship grant. We would like to thank the personnel of the genomic core of the Duke Molecular Physiology Institute (DMPI) and most importantly the participants in the study.

Conflict of interest

All the authors declared no competing interests.

Ethical disclosure

Institutional review board approval was obtained from Duke University Medical Center (Durham, NC). We obtained informed consent from parents and assent from children participating in the study.

Supplementary material

467_2015_3203_MOESM1_ESM.pdf (697 kb)
ESM 1 (PDF 697 kb)

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Copyright information

© IPNA 2015

Authors and Affiliations

  • Shan Elahi
    • 1
  • Alison Homstad
    • 1
    • 2
  • Himani Vaidya
    • 1
    • 2
  • Jennifer Stout
    • 1
  • Gentzon Hall
    • 2
    • 3
  • Guanghong Wu
    • 2
    • 3
  • Peter ConlonJr
    • 1
  • Jonathan C. Routh
    • 1
    • 4
  • John S. Wiener
    • 1
    • 4
  • Sherry S. Ross
    • 4
    • 5
  • Shashi Nagaraj
    • 1
  • Delbert Wigfall
    • 1
  • John Foreman
    • 1
  • Adebowale Adeyemo
    • 6
  • Indra R. Gupta
    • 7
  • Patrick D. Brophy
    • 8
  • C. Egla Rabinovich
    • 1
  • Rasheed A. Gbadegesin
    • 1
    • 2
  1. 1.Department of PediatricsDuke University Medical CenterDurhamUSA
  2. 2.Duke Molecular Physiology InstituteDurhamUSA
  3. 3.Department of MedicineDuke University Medical CenterDurhamUSA
  4. 4.Department of Surgery, Division of UrologyDuke University Medical CenterDurhamUSA
  5. 5.Department of Urology, Pediatric Urology, UNC School of Medicine University of North Carolina at Chapel HillChapel HillUSA
  6. 6.Center for Research on Genomics and Global Health, National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA
  7. 7.Department of Pediatrics and Human GeneticsMcGill UniversityMontrealCanada
  8. 8.Department of PediatricsUniversity of IowaIowa CityUSA

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