Journal article
TNXB Mutations Can Cause Vesicoureteral Reflux
Journal of the American Society of Nephrology, Vol.24(8), pp.1313-1322
07/31/2013
DOI: 10.1681/ASN.2012121148
PMCID: PMC3736717
PMID: 23620400
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.
Details
- Title: Subtitle
- TNXB Mutations Can Cause Vesicoureteral Reflux
- Creators
- Rasheed A Gbadegesin - Divisions ofPatrick D Brophy - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaAdebowale Adeyemo - Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MarylandGentzon Hall - Center for Human Genetics, Duke University Medical Center, Durham, North CarolinaIndra R Gupta - Department of Pediatrics and Human Genetics, McGill University, Montreal, Quebec, CanadaDavid Hains - Department of Pediatrics, The Research Institute at Nationwide Children's Hospital, Columbus, OhioBartlomeij Bartkowiak - Divisions ofC. Egla Rabinovich - Rheumatology, Department of Pediatrics, Duke University Medical Center, Durham, North CarolinaSettara Chandrasekharappa - Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MarylandAlison Homstad - Divisions ofKatherine Westreich - Divisions ofGuanghong Wu - Center for Human Genetics, Duke University Medical Center, Durham, North CarolinaYutao Liu - Center for Human Genetics, Duke University Medical Center, Durham, North CarolinaDanniele Holanda - Department of Pathology, University of Iowa College of Medicine, Iowa City, IowaJason Clarke - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, IowaPeter Lavin - Center for Human Genetics, Duke University Medical Center, Durham, North CarolinaAngelica Selim - Pathology, Duke University Medical Center, Durham, North CarolinaSara Miller - Pathology, Duke University Medical Center, Durham, North CarolinaJohn S Wiener - Division of Urologic Surgery, Department of Surgery and Pediatrics, Duke University Medical Center, Durham, North CarolinaSherry S Ross - Division of Urologic Surgery, Department of Surgery and Pediatrics, Duke University Medical Center, Durham, North CarolinaJohn Foreman - Divisions ofCharles Rotimi - Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MarylandMichelle P Winn - Center for Human Genetics, Duke University Medical Center, Durham, North Carolina
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.24(8), pp.1313-1322
- Publisher
- American Society of Nephrology
- DOI
- 10.1681/ASN.2012121148
- PMID
- 23620400
- PMCID
- PMC3736717
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Language
- English
- Date published
- 07/31/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047697402771
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