A novel mutation in the human voltage-gated potassium channel gene (Kv1.1)associates with episodic ataxia type 1 and sometimes with partial epilepsy

Episodic ataxia type 1 (EA1) is a rare autosomal dominant disorder characte rized by brief episodes of ataxia associated with continuous interattack my okymia, Point mutations in the human voltage-gated potassium channel (Kv1.1 ) gene on chromosome 12p13 have recently been shown to associate with EA1, A Scottish family with EA1 harbouring a novel mutation in this gene is repo rted, Of the five affected individuals over three generations, two had part ial epilepsy in addition to EA1, The detailed clinical, electrophysiologica l and molecular genetic findings are presented, The heterozygous point muta tion is located at nucleotide position 677 and results in a radical amino a cid substitution at a highly conserved position in the Second transmembrane domain of the potassium channel, Functional studies indicated that mutant subunits exhibited a dominant negative effect on potassium channel function and would be predicted to impair neuronal repolarization, Potassium channe ls determine the excitability of neurons and blocking drugs are proconvulsa nt. A critical review of previously reported EA1 families shows an over-rep resentation of epilepsy in family members with EA1 compared with unaffected members, These observations indicate that this mutation is pathogenic and suggest that the epilepsy in EA1 may be caused by the dysfunctional potassi um channel, It is possible that such dysfunction may be relevant to other e pilepsies in man.