Remapping and mutation analysis of benign adult familial myoclonic epilepsy in a Japanese pedigree

Benign adult familial myoclonic epilepsy (BAFME), alternatively named familial adult myoclonic epilepsy 1/familial cortical myoclonic tremor with epilepsy 1 (FAME1/FCMTE1), is a hereditary epileptic syndrome characterized by autosomal dominant inheritance, adult-onset tremulous hand movement, myoclonus, infrequent epileptic seizure and non-progressive course without cerebellar ataxia and dementia. We previously reported evidence for linkage of BAFME to the region between D8S1784 and D8S1694 on chromosome 8q. Subsequently, other research groups reported mapping of the same clinical syndrome to different chromosomal loci, 2p and 5p, in Italian (FAME2/FCMTE2) and French (FAME3/FCMTE3) families, respectively. In this study, we performed a genome-wide linkage analysis using 10K single-nucleotide polymorphism arrays and additional microsatellite markers to reconfirm the BAFME-linked region. The BAFME-linked region was mapped to 7.16 Mb spanned by rs1898287 and rs2891799 on chromosomes 8q23.3–8q24.13 with a maximum two-point logarithm of odds score of 6.0 for the marker rs1021897. Sequence analysis and copy-number variant analysis of all 38 genes localized in the candidate region were performed, but no pathogenic mutation was identified. We conclude that the etiology of BAFME remains to be solved, and further genetic studies, which may require analysis in non-coding regions of a gene, introns or intergenic spacer regions, are necessary to reveal its unknown mutations.