Functional analysis of the A322D mutation in the GABA(A) receptor alpha1 subunit associated with juvenile myoclonic epilepsy

Background: Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies (IGE). Although the mode of inheritance is usually complex, in some families it appears to be autosomal dominant with a major gene effect of a single mutation. The first mutation in such a three generation JME family was detected recently in the alpha1 subunit of the GABA(A) receptor, predicting the single amino acid substitution A322D (GABRA1, Cossette et al. Nat Gen 2002;31:184–9). Methods: We now studied the functional consequences of this mutation using co-expression of…