Localization Of A Chinese Familial Cortical Myoclonic Tremor With Epilepsy Pedigree

Background:Familial cortical myoclonic tremor with epilepsy (FCMTE) is a kind of autosomal dominant epilepsy syndrome with considerable clinical and genetic heterogeneity. Its major clinical manifestations include adult onset, cortical myoclonic tremor, with or without epileptic seizures. Four loci,8q24 (FCMTE1),2p11.1-q12.2 (FCMTE2),5p15.31-p15.1 (FCMTE3) and 3q26.32-3q28 (FCMTE4) were previously reported with only one gene-a2B adrenergic receptor-being identified in two FCMTE2 pedigrees.Objective:To identify the region of the causative gene in a Chinese FCMTE pedigree.Methods:We did clinical and electrophysiologic examinations in a Chinese FCMTE pedigree. Whole genome scan was performed by using Illumina Human Omini ZhongHua-8 BeadChip. Linkage analysis and haplotype analysis were done to identify the causative gene region.Results:There were 12 patients alive in this FCMTE pedigree.9 patients had both cortical myoclonic tremor and epilepsy and 3 patients had only cortical myoclonic tremor. The mean onset age of tremor was 34.3 (13-36) years old and 34.3 (29-40) years old for epilepsy. Electrophysiologic examinations showed giant somatosensory evoked potentials (g-SEP) and long-latency cortical reflex (LLCR or C-reflex) in some patients. Linkage analysis showed 322 peaks covering 26.6 Mb of genomic DNA on chromosome 8 with a two-point LOD score> 3.0 (the range of scores was 3.170-3.766 with a top LOD score of 3.766 at 206 single nucleotide polymorphisms (SNPs). Haplotype analysis revealed that all patients share a common haplotype from rs7001897 to rs10093411, about 20.4 Mb on 8q22.3-q24.13.Conclusion:We report a Chinese FCMTE1 pedigree localized on 8q22.3-q24.13, which shares the same region with Japan’s pedigrees. Whole-exome sequencing and targeted-genome sequencing need to do to identify the causative gene for FCMTE1.