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J Am Soc Nephrol. 2014 Aug;25(8):1653-61. doi: 10.1681/ASN.2013060646. Epub 2014 Mar 7.

Mutations in ANKS6 cause a nephronophthisis-like phenotype with ESRD.

Author information

1
Nephrogenetics Laboratory, andDepartments of Medical Genetics.
2
Nephrogenetics Laboratory, and.
3
Pediatric Pathology.
4
Histology and Embryology, and.
5
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri;
6
Department of Internal Medicine, and.
7
**Department of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey;
8
Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
9
Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;
10
Department of Internal Medicine, andEugene McDermott Center for Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas;
11
Center for Human Genetics, Bioscientia, Ingelheim, Germany; Department of Nephrology and Center for Clinical Research, University Hospital, Freiburg, Germany; and.
12
Nephrogenetics Laboratory, andPediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey; Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey fozaltin@hacettepe.edu.tr.

Abstract

Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active β-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.

KEYWORDS:

chronic renal failure; end stage kidney disease; end stage renal disease; familial nephropathy; genetic renal disease

PMID:
24610927
PMCID:
PMC4116054
DOI:
10.1681/ASN.2013060646
[Indexed for MEDLINE]
Free PMC Article

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