The gene encoding the alpha1A-voltage-dependent calcium channel (CACN1A4) is not a candidate for causing common subtypes of idiopathic generalized epilepsy.

Mutations in the gene encoding the alpha1A-calcium channel subunit play a causative role in the epileptogenesis of absence seizures in tottering mutant mice. The present family-based association and non-parametric linkage study tested the hypothesis that allelic variants of the homologous human gene (CACN1A4) confer susceptibility to common subtypes of idiopathic generalized epilepsy (IGE). An expressed polymorphic CAG trinucleotide repeat in the 3' end of the CACN1A4 gene was assessed in 70 families ascertained through members with either childhood (CAE) and juvenile absence epilepsy (JAE), or juvenile myoclonic epilepsy (JME). Our association analysis using the haplotype-based haplotype relative risk statistic provided no evidence for an allelic association of the CAG repeat polymorphism with either IGE, or CAE and JAE, or JME. We found no relation between the CAG repeat length and susceptibility neither to IGE, nor to CAE and JAE, nor to JME. Non-parametric linkage analysis revealed no evidence for linkage of IGE traits with the CACN1A4 locus in 42 families of patients with either CAE or JAE. A weak trend towards an excess of allele sharing (identity by descent) among family members affected by an IGE was obtained in 26 families of JME patients (Z[NPL] = 1.25 at theta = 0.000, p = 0.057). Taken together, we found no statistically significant evidence that genetic variants of the CACN1A4 gene play a causative role in the pathogenesis of common subtypes of IGE in humans.