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Acidosis and Deafness in Patients with Recessive Mutations in FOXI1

Enerbäck, S; Nilsson, D; Edwards, N; Heglind, M; Alkanderi, S; Ashton, E; Deeb, A; ... Sayer, JA; + view all (2018) Acidosis and Deafness in Patients with Recessive Mutations in FOXI1. Journal of the American Society of Nephrology , 29 (3) pp. 1041-1048. 10.1681/ASN.2017080840. Green open access

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Abstract

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 acidbase 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.

Type: Article
Title: Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1681/ASN.2017080840
Publisher version: http://dx.doi.org/10.1681/ASN.2017080840
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: chronic metabolic acidosis, genetic renal disease, ion transport
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10042823
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