Localization Of A Familial Cortical Myoclonic Tremor With Epilepsy Pedigree

Background:Familial cortical myoclonic tremor with epilepsy(FCMTE)is an autosomal dominant inherited disorder characterized by adult onset,cortical myoclonic tremor predominantly in the upper limbs,with or without epileptic seizures and a benign course without cerebral ataxia or dementia.Since 1990(FCMTE was first descripted),more than 80 pedigrees have been reported.Genetic studies have identified four loci responsible for FCMTE:FCMTE1(8q22.3-q24.13),FCMTE2(2p11.2-q12.2),FCMTE3(5p15.31-p15.1)and FCMTE4(3q26.32-3q28).Among these loci,ADRA2B gene was the only gene identified to be possibly causative in two FCMTE2 pedigrees.Objective:To identify the causative gene region of a new Chinese FCMTE pedigree.Methods:Detailed clinical and electrophysiological data of a new Chinese FCMTE pedigree were obtained.Illumina Human Omini ZhongHua-8 BeadChip was used for whole genome scan in 20 selected pedigree members.Linkage analysis and haplotype analysis were performed to identify the causative locus.Results:There were 10 patients alive in this FCMTE pedigree.Eight patients presented with both cortical myoclonic tremor and epilepsy,2 patients only presented with cortical myoclonic tremor.The mean age at onset of tremor and epilepsy was 28(9-45)years and 36(31-42)years,respectively.Linkage analysis showed 12 peaks covering a 17.4 Mb region on chromosome 8 with a two-point LOD score>3.0(the maximum LOD score is 3.185).Haplotype analysis revealed that all patients shared a common haplotype,a 20.25 Mb interval between rs506389 and rs12544067 markers on chromosome 8q22.3-q24.13.Conclusion:We identified a new Chinese FCMTE1 pedigree,with genetic mapping to the same chromosomal region(8q22.3-q24.13)as previously reported from Japan and China.Whole-exome sequencing and targeted-genome sequencing are required for further identification of the causative gene for FCMTE1.