Schlingmann, Karl P. and Renigunta, Aparna and Hoorn, Ewout J. and Forst, Anna-Lena and Renigunta, Vijay and Atanasov, Velko and Mahendran, Sinthura and Barakat, Tahsin Stefan and Gillion, Valentine and Godefroid, Nathalie and Brooks, Alice S. and Lugtenberg, Dorien and Lake, Jennifer and Debaix, Huguette and Rudin, Christoph and Knebelmann, Bertrand and Tellier, Stephanie and Rousset-Rouviere, Caroline and Viering, Daan and de Baaij, Jeroen H. F. and Weber, Stefanie and Palygin, Oleg and Staruschenko, Alexander and Kleta, Robert and Houillier, Pascal and Bockenhauer, Detlef and Devuyst, Olivier and Vargas-Poussou, Rosa and Warth, Richard and Zdebik, Anselm A. and Konrad, Martin (2021) Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 32 (6). pp. 1498-1512. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)Abstract
Background The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+,K+-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness. Methods A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. Results We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents. Conclusions Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DISTAL CONVOLUTED TUBULE; RECTIFYING K+ CHANNEL; BASOLATERAL MEMBRANE; NACL COTRANSPORTER; POTASSIUM CHANNELS; KIR5.1; MUTATIONS; KIR4.1; EXPRESSION; LOCALIZATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 14:03 |
| Last Modified: | 30 Sep 2022 14:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48153 |
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