Published January 1, 2014
| Version v1
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Mutations in ANKS6 Cause a Nephronophthisis-Like Phenotype with ESRD
Creators
- 1. Hacettepe Univ, Fac Med, Nephrogenet Lab, TR-06100 Ankara, Turkey
- 2. Hacettepe Univ, Fac Med, Dept Pediat Pathol, TR-06100 Ankara, Turkey
- 3. Hacettepe Univ, Fac Med, Dept Histol & Embryol, TR-06100 Ankara, Turkey
- 4. Univ Missouri, Coll Vet Med, Dept Vet Pathobiol, Columbia, MO USA
- 5. Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
- 6. Istanbul Medeniyet Univ, Dept Pediat Nephrol, Istanbul, Turkey
- 7. Hacettepe Univ, Fac Med, Dept Pediat Nephrol, TR-06100 Ankara, Turkey
- 8. Ctr Pediat & Adolescent Med, Pediat Nephrol Div, Heidelberg, Germany
Description
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 beta-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.
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