Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations
New England Journal of Medicine, Volume 360, No. 19, Year 2009
Notification
URL copied to clipboard!
Description
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. Copyright © 2009 Massachusetts Medical Society.
Authors & Co-Authors
Böckenhauer, Detlef
United Kingdom, London
University College London
Feather, Sally A.
United Kingdom, Leeds
University of Leeds
Stanescu, Horia C.
United Kingdom, London
University College London
United States, Bethesda
National Institutes of Health Nih
Bandulik, Sascha
Germany, Regensburg
Universität Regensburg
Zdebik, Anselm A.
United Kingdom, London
University College London
Reichold, Markus
Germany, Regensburg
Universität Regensburg
Tobin, Jonathan
United Kingdom, London
University College London
Lieberer, Evelyn
Germany, Regensburg
Universität Regensburg
Sterner, Christina
Germany, Regensburg
Universität Regensburg
Landouré, Guida
United Kingdom, London
University College London
United States, Bethesda
National Institutes of Health Nih
Mali, Bamako
University of Bamako
Arora, Ruchi
United Kingdom, London
University College London
Sirimanna, Tony
United Kingdom, London
University College London
Thompson, Dorothy A.
United Kingdom, London
University College London
Cross, J. Helen
United Kingdom, London
University College London
van’t Hoff, William G.
United Kingdom, London
University College London
Al-Masri, Omar
United Arab Emirates, Abu Dhabi
Sheikh Khalifa Medical City
Tullus, Kjell
United Kingdom, London
University College London
Yeung, Stella
United Kingdom, Leeds
University of Leeds
Anikster, Yair
United States, Bethesda
National Institutes of Health Nih
Israel, Tel Hashomer Tel Aviv
Chaim Sheba Medical Center Israel
Klootwijk, Enriko
United Kingdom, London
University College London
United States, Bethesda
National Institutes of Health Nih
Hubank, Mike
United Kingdom, London
University College London
Dillon, Michael J.
United Kingdom, London
University College London
Heitzmann, Dirk
Germany, Regensburg
Universität Regensburg
Arcos-Burgos, Mauricio
United States, Bethesda
National Institutes of Health Nih
United States, Coral Gables
University of Miami
Knepper, Mark A.
United States, Bethesda
National Institutes of Health Nih
Dobbie, Angus
United Kingdom, Leeds
University of Leeds
Gahl, William Allen
United States, Bethesda
National Institutes of Health Nih
Warth, R.
Germany, Regensburg
Universität Regensburg
Sheridan, Eamonn G.
United Kingdom, Leeds
University of Leeds
Kleta, Robert
United Kingdom, London
University College London
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 501
Authors: 30
Affiliations: 8
Identifiers
Doi:
10.1056/NEJMoa0810276
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases