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 least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K⁺ channel genes are candidate genes for EA, we tested markers near known K⁺ channel genes for linkage. Using a group of Genethon markers from one such region-chromosome 12p-we found evidence of linkage in four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at θ = 0, with the marker D12S99. A human Ca⁺⁺ channel gene, CACNL1A1, and three human K⁺ channel genes-KCNA5, KCNA6, and KCNA1-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 between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.