TNXB mutations can cause vesicoureteral reflux

Rasheed A. Gbadegesin, Patrick D. Brophy, Adebowale Adeyemo, Gentzon Hall, Indra R. Gupta, David Hains, Bartlomeij Bartkowiak, C. Egla Rabinovich, Settara Chandrasekharappa, Alison Homstad, Katherine Westreich, Guanghong Wu, Yutao Liu, Danniele Holanda, Jason Clarke, Peter Lavin, Angelica Selim, Sara Miller, John S. Wiener, Sherry S. Ross & 3 others John Foreman, Charles Rotimi, Michelle P. Winn

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Primary vesicoureteral reflux (VUR) is the most common congenital anomaly of the kidney and the urinary tract, and it is a major risk factor for pyelonephritic scarring and CKD in children. Although twin studies support the heritability of VUR, specific genetic causes remain elusive. We performed a sequential genome-wide linkage study and whole-exome sequencing in a family with hereditary VUR. We obtained a significant multipoint parametric logarithm of odds score of 3.3 on chromosome 6p, and whole-exome sequencing identified a deleterious heterozygous mutation (T3257I) in the gene encoding tenascin XB (TNXB in 6p21.3). This mutation segregated with disease in the affected family as well as with a pathogenic G1331R change in another family. Fibroblast cell lines carrying the T3257I mutation exhibited a reduction in both cell motility and phosphorylated focal adhesion kinase expression, suggesting a defect in the focal adhesions that link the cell cytoplasm to the extracellular matrix. Immunohistochemical studies revealed that the human uroepithelial lining of the ureterovesical junction expresses TNXB, suggesting that TNXB may be important for generating tensile forces that close the ureterovesical junction during voiding. Taken together, these results suggest that mutations in TNXB can cause hereditary VUR.

Original languageEnglish (US)
Pages (from-to)1313-1322
Number of pages10
JournalJournal of the American Society of Nephrology
Volume24
Issue number8
DOIs
StatePublished - Jul 31 2013

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Vesico-Ureteral Reflux
Exome
Mutation
Tenascin
Focal Adhesion Protein-Tyrosine Kinases
Twin Studies
Focal Adhesions
Cell Movement
Cicatrix
Extracellular Matrix
Cytoplasm
Fibroblasts
Chromosomes
Genome
Cell Line
Genes

ASJC Scopus subject areas

  • Nephrology

Cite this

Gbadegesin, R. A., Brophy, P. D., Adeyemo, A., Hall, G., Gupta, I. R., Hains, D., ... Winn, M. P. (2013). TNXB mutations can cause vesicoureteral reflux. Journal of the American Society of Nephrology, 24(8), 1313-1322. https://doi.org/10.1681/ASN.2012121148

TNXB mutations can cause vesicoureteral reflux. / Gbadegesin, Rasheed A.; Brophy, Patrick D.; Adeyemo, Adebowale; Hall, Gentzon; Gupta, Indra R.; Hains, David; Bartkowiak, Bartlomeij; Rabinovich, C. Egla; Chandrasekharappa, Settara; Homstad, Alison; Westreich, Katherine; Wu, Guanghong; Liu, Yutao; Holanda, Danniele; Clarke, Jason; Lavin, Peter; Selim, Angelica; Miller, Sara; Wiener, John S.; Ross, Sherry S.; Foreman, John; Rotimi, Charles; Winn, Michelle P.

In: Journal of the American Society of Nephrology, Vol. 24, No. 8, 31.07.2013, p. 1313-1322.

Research output: Contribution to journalArticle

Gbadegesin, RA, Brophy, PD, Adeyemo, A, Hall, G, Gupta, IR, Hains, D, Bartkowiak, B, Rabinovich, CE, Chandrasekharappa, S, Homstad, A, Westreich, K, Wu, G, Liu, Y, Holanda, D, Clarke, J, Lavin, P, Selim, A, Miller, S, Wiener, JS, Ross, SS, Foreman, J, Rotimi, C & Winn, MP 2013, 'TNXB mutations can cause vesicoureteral reflux', Journal of the American Society of Nephrology, vol. 24, no. 8, pp. 1313-1322. https://doi.org/10.1681/ASN.2012121148
Gbadegesin RA, Brophy PD, Adeyemo A, Hall G, Gupta IR, Hains D et al. TNXB mutations can cause vesicoureteral reflux. Journal of the American Society of Nephrology. 2013 Jul 31;24(8):1313-1322. https://doi.org/10.1681/ASN.2012121148
Gbadegesin, Rasheed A. ; Brophy, Patrick D. ; Adeyemo, Adebowale ; Hall, Gentzon ; Gupta, Indra R. ; Hains, David ; Bartkowiak, Bartlomeij ; Rabinovich, C. Egla ; Chandrasekharappa, Settara ; Homstad, Alison ; Westreich, Katherine ; Wu, Guanghong ; Liu, Yutao ; Holanda, Danniele ; Clarke, Jason ; Lavin, Peter ; Selim, Angelica ; Miller, Sara ; Wiener, John S. ; Ross, Sherry S. ; Foreman, John ; Rotimi, Charles ; Winn, Michelle P. / TNXB mutations can cause vesicoureteral reflux. In: Journal of the American Society of Nephrology. 2013 ; Vol. 24, No. 8. pp. 1313-1322.
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AU - Wu, Guanghong

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AU - Winn, Michelle P.

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