Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a distinct form of idiopathic generalized epilepsy (IGE). One of the candidate regions for human JME has been mapped on chromosome band 6p11-p12 by linkage analyses and is termed EJM1 (MIM 254770). Recently, we reported the reduction of the EJM1 region to 3.5cM that contains 18 genes, the exclusion of three genes (LRRC1, GCLC, KIAA0057) by mutation analyses, and the identification of Myoclonin1/EFHC1 as the EJM1 gene. Here, we describe detailed physical and transcriptome maps of the 3.5cM EJM1 region, and detailed results of mutation analyses for the remained 14 genes (HELO1, GCMA, KIAA0936, FBXO9, GSTA3, GSTA4, PTD011, KIAA0576, LMPB1, IL17F, MCM3, PKHD1, KIAA0105, TFAP2B) in patients with JME. We identified 49 single nucleotide changes in eight genes. Twelve amino acid substitutions occurred in two genes, 11 silent mutations in seven genes, and 26 in the non-coding or intronic regions of seven genes. Twelve amino acid substitutions in the two genes (IL17F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members. Thus, the absence of significant and potentially functional mutations in the remaining 14 genes further supports the concept that Myoclonin1/EFHC1 is the EJM1 gene in chromosome 6p12.