A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions.
Arch Neurol
; 59(7): 1137-41, 2002 Jul.
Article
en En
| MEDLINE
| ID: mdl-12117362
ABSTRACT
CONTEXT Missense mutations in the GABRG2 gene, which encodes the gamma 2 subunit of central nervous gamma-aminobutyric acid (GABA)(A) receptors, have recently been described in 2 families with idiopathic epilepsy. In one of these families, the affected individuals predominantly exhibited childhood absence epilepsy and febrile convulsions. OBJECTIVE:
To assess the role of GABRG2 in the genetic predisposition to idiopathic absence epilepsies.DESIGN:
The GABRG2 gene was screened by single-strand conformation analysis for mutations. Furthermore, a population-based association study assessing a common exon 5 polymorphism (C588T) was carried out. PATIENTS The sample was composed of 135 patients with idiopathic absence epilepsy and 154 unrelated and ethnically matched controls.RESULTS:
A point mutation (IVS6 + 2T-->G) leading to a splice-donor site mutation in intron 6 was found. The mutation, which is predicted to lead to a nonfunctional protein, cosegregates with the disease status in a family with childhood absence epilepsy and febrile convulsions. The association study did not find any significant differences in the allele and genotype frequencies of the common exon 5 polymorphism (C588T) between patients with idiopathic absence epilepsy and controls (P>.35).CONCLUSIONS:
Our study identified a splice-donor-site mutation that was probably causing a nonfunctional GABRG2 subunit. This mutation occurred in heterozygosity in the affected members of a single nuclear family, exhibiting a phenotypic spectrum of childhood absence epilepsy and febrile convulsions. The GABRG2 gene seems to confer a rare rather than a frequent major susceptibility effect to common idiopathic absence epilepsy syndromes.
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Banco de datos:
MEDLINE
Asunto principal:
Epilepsia Tipo Ausencia
/
Receptores de GABA-A
/
Convulsiones Febriles
/
Mutación Missense
Tipo de estudio:
Risk_factors_studies
Límite:
Adolescent
/
Female
/
Humans
/
Male
Idioma:
En
Año:
2002
Tipo del documento:
Article