title: Mutations in ANKS6 cause a nephronophthisis-like phenotype with ESRD.
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.
authors.affiliation: Nephrogenetics Laboratory, andDepartments of Medical Genetics.
authors.forename: Ekim Z
authors.initials: EZ
authors.lastname: Taskiran
authors.affiliation: Nephrogenetics Laboratory, and.
authors.forename: Emine
authors.initials: E
authors.lastname: Korkmaz
authors.affiliation: Pediatric Pathology.
authors.forename: Safak
authors.initials: S
authors.lastname: Gucer
authors.affiliation: Nephrogenetics Laboratory, and.
authors.forename: Can
authors.initials: C
authors.lastname: Kosukcu
authors.affiliation: Histology and Embryology, and.
authors.forename: Figen
authors.initials: F
authors.lastname: Kaymaz
authors.affiliation: Nephrogenetics Laboratory, and.
authors.forename: Cansu
authors.initials: C
authors.lastname: Koyunlar
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri;
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Bryda
authors.affiliation: Department of Internal Medicine, and.
authors.forename: Moumita
authors.initials: M
authors.lastname: Chaki
authors.affiliation: Department of Internal Medicine, and.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, and.
authors.forename: Komal
authors.initials: K
authors.lastname: Vadnagara
authors.affiliation: **Department of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey;
authors.forename: Cengiz
authors.initials: C
authors.lastname: Candan
authors.affiliation: Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey;
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.affiliation: Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
authors.affiliation: Department of Internal Medicine, andEugene McDermott Center for Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Massimo
authors.initials: M
authors.lastname: Attanasio
authors.affiliation: Center for Human Genetics, Bioscientia, Ingelheim, Germany; Department of Nephrology and Center for Clinical Research, University Hospital, Freiburg, Germany; and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.affiliation: Nephrogenetics Laboratory, andPediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey; Hacettepe University Center for Biobanking and Genomics, Ankara, Turkey fozaltin@hacettepe.edu.tr.
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014421:Turkey
chemical_list: C532258:ANKS6 protein, human; D009687:Nuclear Proteins
keywords: chronic renal failure; end stage kidney disease; end stage renal disease; familial nephropathy; genetic renal disease