Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations.

Authors: Bockenhauer, D  Feather, S  Stanescu, HC  Bandulik, S  Zdebik, AA  Reichold, M  Tobin, J  Lieberer, E  Sterner, C  Landoure, G  Arora, R  Sirimanna, T  Thompson, D  Cross, JH  Van't Hoff, W  Al Masri, O  Tullus, K  Yeung, S  Anikster, Y  Klootwijk, E  Hubank, M  Dillon, MJ  Heitzmann, D  Arcos-Burgos, M  Knepper, MA  Dobbie, A  Gahl, WA  Warth, R  Sheridan, E  Kleta, R 
Citation: Bockenhauer D, etal., N Engl J Med. 2009 May 7;360(19):1960-70. doi: 10.1056/NEJMoa0810276.
Pubmed: (View Article at PubMed) PMID:19420365
DOI: Full-text: DOI:10.1056/NEJMoa0810276

BACKGROUND: Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy). METHODS: Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice. RESULTS: Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting. CONCLUSIONS: Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.


Disease Annotations
Phenotype Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 8662866
Created: 2014-06-25
Species: All species
Last Modified: 2014-06-25
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.