A GENE FOR EPISODIC ATAXIA MYOKYMIA MAPS TO CHROMOSOME 12P13/

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at leas t two distinct clinical syndromes. One clinical type of EA (MIM 160120 ) includes individuals who have episodes of ataxia and dysarthria last ing seconds to minutes. In addition, myokymia (rippling of muscles, di agnosable by electromyography) is evident during and between attacks. Since Kf channel genes are candidate genes for EA, we tested markers n ear known Kf channel genes for linkage. Using a group of Genethon mark ers from one such region-chromosome 12p-we found evidence of linkage i n four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel ge ne, CACNL1A1, and three human K+ channel genes-KCNA5, KCNA6, and KCNAl -map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur bet ween the disease gene and a CA-repeat marker located close to this gen e. Studies of a large Ed family with a different clinical phenotype (M IM 108500), which lacks myokymia but is associated with nystagmus, hav e excluded the gene causing that disease from the chromosome 12p locus .