|
Title
|
|
|
|
Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes
| |
|
Author
|
|
|
|
| |
|
Institution/Organisation
|
|
|
|
EuroEPINOMICS RES Consortium
| |
|
Abstract
|
|
|
|
| Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Nature genetics. - New York, N.Y.
| |
|
Publication
|
|
|
|
New York, N.Y.
:
2014
| |
|
ISSN
|
|
|
|
1061-4036
| |
|
DOI
|
|
|
|
10.1038/NG.3130
| |
|
Volume/pages
|
|
|
|
46
:12
(2014)
, p. 1327-1332
| |
|
ISI
|
|
|
|
000345547300014
| |
|
Pubmed ID
|
|
|
|
25362483
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|