Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy

Simons Cas, Rash, Lachlan D., Crawford, Joanna, Ma, Linlin, Cristofori-Armstrong, Ben, Miller, David, Ru, Kelin, Baillie, Gregory J., Alanay, Yasemin, Jacquinet, Adeline, Debray, François-Guillaume, Verloes, Alain, Shen, Joseph, Yesil, Gözde, Guler, Serhat, Yuksel, Adnan, Cleary, John G., Grimmond, Sean M., McGaughran, Julie, King, Glenn F., Gabbett, Michael T. and Taft, Ryan J. (2015) Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy. Nature Genetics, 47 1: 73-77. doi:10.1038/ng.3153

Author Simons Cas
Rash, Lachlan D.
Crawford, Joanna
Ma, Linlin
Cristofori-Armstrong, Ben
Miller, David
Ru, Kelin
Baillie, Gregory J.
Alanay, Yasemin
Jacquinet, Adeline
Debray, François-Guillaume
Verloes, Alain
Shen, Joseph
Yesil, Gözde
Guler, Serhat
Yuksel, Adnan
Cleary, John G.
Grimmond, Sean M.
McGaughran, Julie
King, Glenn F.
Gabbett, Michael T.
Taft, Ryan J.
Title Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
Publication date 2015-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ng.3153
Open Access Status Not Open Access
Volume 47
Issue 1
Start page 73
End page 77
Total pages 5
Place of publication New York, United States
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six individuals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 24 November 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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