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Lookup NU author(s): Dr Noel Edwards, Sumaya Alkanderi, Professor John SayerORCiD
Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
Author(s): Enerbäck S, Nilsson D, Edwards N, Heglind M, Alkanderi S, Ashton E, Deeb A, Kokash FEB, Bakhsh ARA, Van'tHoff W, Walsh SB, D'Arco F, Daryadel A, Bourgeois S, Wagner CA, Kleta R, Bockenhauer D, Sayer JA
Publication type: Article
Publication status: Published
Journal: Journal of the American Society of Nephrology
Year: 2018
Volume: 29
Issue: 3
Pages: 1041-1048
Print publication date: 01/03/2018
Online publication date: 14/12/2017
Acceptance date: 14/12/2017
Date deposited: 08/01/2018
ISSN (print): 1046-6673
ISSN (electronic): 1533-3450
Publisher: American Society of Nephrology
URL: https://doi.org/10.1681/ASN.2017080840
DOI: 10.1681/ASN.2017080840
PubMed id: 29242249
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