Abstracts

Mutations in genes encoding the gamma 2 (GABRG2) and alpha 1 (GABRA1) subunits of the GABA(A) receptor have been found to predispose to childhood absence epilepsy (CAE) and juvenile myoclonic epilepsy (JME) in large kindreds. Whether these genes could also predispose to a significant proportion of idiopathic generalized epilepsy (IGE) cases remains to be determined.
We genotyped 150 unrelated IGE individuals, mostly of French-Canadian origin, using 6 informative microsatellite markers spanning the GABA(A) receptor gene cluster on chromosome 5q34. Allelic distributions were compared between three different groups of IGE individuals (all IGE, n = 150; CAE, n=50; and JME/JAE, n=38) and 100 controls of French-Canadian origin. The affected individuals were also screened for mutation in GABRG2, and GABRA1, using SSCP and dHPLC techniques.
We did not find significant difference in the allelic distribution between the three groups of affected individuals and controls. However, when compared to controls, a significant increase in an allele frequency was observed for marker D5S403 (chi(2)=5.34, df=1, p=0.02) and D5S422 (chi(2)=4.74, df=1, p=0.03), respectively in the IGE and CAE group. In addition, a trend toward an excess of an allele was observed for two additional markers in the IGE group (D5S422: chi(2)=3. 19, df=1, p=0.07; and D5S2066: chi(2)=3. 27, df=1, p=0.07), as well as in the CAE group (D5S403: chi(2)=3. 59, df=1, p=0.06; and D5S1456: chi(2)=3. 72, df=1, p=0.05). No association was found for the JME/JAE group. We did not find mutation in the coding regions of GABRG2 and GABRA1.
These results provide evidence for an association between the GABA(A) receptor gene cluster on chromosome 5q34 and CAE in the French-Canadian population. The absence of mutation in GABRG2 and GABRA1 raises the possibility that another GABA(A) gene mapping to this locus is involved in this common epileptic syndrome.
[Supported by: Canadian Institutes for Health Research to PC and GAR.]