Intronic pentanucleotide TTTCA repeat insertion in SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1
作者单位：Department of Neurology Second Affiliated Hospital School of Medicine Zhejiang University Intensive Care Unit Zhejiang Hospital Department of Neurology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Department of Neurology Ruijin Hospital School of Medicine Shanghai Jiao Tong University Department of Neurology Zhejiang Hospital Department of Neurology Lishui People’s Hospital Cancer Institute Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Second Affiliated Hospital School of Medicine Zhejiang University Department of Neurology Faculty of Medicine The University of Tokyo Department of Molecular Neurology Graduate School of Medicine The University of Tokyo International University of Health and Welfare Graduate School Center for Medical Genetics School of Life Sciences Central South University Department of Psychiatry SUNY Upstate Medical University Department of Neurology University of Tennessee Health Science Center
会议名称：《2018年浙江省神经病学学术年会》
会议日期：2018年
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
摘 要：Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes(type 1-4) mapped on different chromosomes(8 q24, 2 p11.1-q12.2, 5 p15.31-p15.1 and 5 p15.31-p15.1) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of twenty Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point LOD scores from 1.64 to 3.77(LOD scores in 5 pedigrees were 3.0) in chromosomal region 8 q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range PCR and repeat-primed PCR, we identified an intronic pentanucleotide(TTTCA)n insertion in SAMD12 gene as the cause, which was cosegregated with the disease among the 11 pedigrees mapped on 8 q24 and additional 7 un-mapped pedigrees. Only 2 pedigrees did not detect this(TTTCA)n insertion. Repeat-primed PCR revealed that the sizes of(TTTCA)n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion(ATTTCATTTC) 58 has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.