A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions

Item Type:	Article
Title:	A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions
Creators Name:	Kananura, C. and Haug, K. and Sander, T. and Runge, U. and Gu, W. and Hallmann, K. and Rebstock, J. and Heils, A. and Steinlein, O.K.
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.
Keywords:	Absence Epilepsy, Alleles, Exons, Febrile Seizures, GABA-A Receptors, Genetic Polymorphism, Genotype, Missense Mutation, Reverse Transcriptase Polymerase Chain Reaction
Source:	Archives of Neurology
ISSN:	0003-9942
Volume:	59
Number:	7
Page Range:	1137-1141
Date:	July 2002
Official Publication:	https://doi.org/10.1001/archneur.59.7.1137
PubMed:	View item in PubMed

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