Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies.
Nat Genet
; 33(4): 527-32, 2003 Apr.
Article
em En
| MEDLINE
| ID: mdl-12612585
ABSTRACT
Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Epilepsia Generalizada
/
Canais de Cloreto
/
Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article