Lehong Gao1, Liping Li1, Jing Ye1, Xilin Zhu2, Ning Shen2, Xiating Zhang1, Dequan Wang1, Yu Gao1, Hua Lin1, Yuping Wang3, Ying Liu4. 1. Department of Neurology, Xuanwu Hospital, Capital Medical University, The Beijing Key Laboratory of Neuromodulation, Beijing 100053, China. 2. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100101, China. 3. Department of Neurology, Xuanwu Hospital, Capital Medical University, The Beijing Key Laboratory of Neuromodulation, Beijing 100053, China. Electronic address: doctorwangyuping@163.com. 4. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100101, China. Electronic address: liuyingpumc@163.com.
Abstract
PURPOSE: Familial cortical myoclonic tremor with epilepsy (FCMTE) is an epileptic syndrome with autosomal dominant inheritance, of which four genetic subtypes (FCMTE1-4) have been reported. In the present study, we described the clinical and neurophysiologic features of a newly diagnosed Chinese FCMTE family, and investigated the genetic cause for this disease. METHODS: Clinical information was obtained from affected and normal individuals of an FCMTE family comprising 41 members. Electroencephalographies were analyzed in five of six affected members (including the proband). Brain magnetic resonance imaging, somatosensory evoked potential with C-reflex analysis and magnetoencephalography was performed in the proband. Genomic DNA of three affected and two unaffected individuals was analyzed to detect the genetic mutations by using whole-exome sequencing. RESULTS: The inheritance pattern of the pedigree was autosomal dominant. A novel missense mutation c.475C>T (p.Ala159Thr) of PLA2G6 were identified in this family. The mutated locus is highly conserved among other species. The mutation is predicted to have a functional impact, and completely co-segregated with the phenotype. CONCLUSION: This study identifies a novel PLA2G6 mutation that is the possible genetic cause of FCMTE in this family. This mutation and associated clinical features expand the spectrum and phenotypes of PLA2G6-related disorders including neurodegenerative diseases.
PURPOSE:Familial cortical myoclonic tremor with epilepsy (FCMTE) is an epileptic syndrome with autosomal dominant inheritance, of which four genetic subtypes (FCMTE1-4) have been reported. In the present study, we described the clinical and neurophysiologic features of a newly diagnosed Chinese FCMTE family, and investigated the genetic cause for this disease. METHODS: Clinical information was obtained from affected and normal individuals of an FCMTE family comprising 41 members. Electroencephalographies were analyzed in five of six affected members (including the proband). Brain magnetic resonance imaging, somatosensory evoked potential with C-reflex analysis and magnetoencephalography was performed in the proband. Genomic DNA of three affected and two unaffected individuals was analyzed to detect the genetic mutations by using whole-exome sequencing. RESULTS: The inheritance pattern of the pedigree was autosomal dominant. A novel missense mutation c.475C>T (p.Ala159Thr) of PLA2G6 were identified in this family. The mutated locus is highly conserved among other species. The mutation is predicted to have a functional impact, and completely co-segregated with the phenotype. CONCLUSION: This study identifies a novel PLA2G6 mutation that is the possible genetic cause of FCMTE in this family. This mutation and associated clinical features expand the spectrum and phenotypes of PLA2G6-related disorders including neurodegenerative diseases.
Authors: Tom van den Ende; Sarvi Sharifi; Sandra M A van der Salm; Anne-Fleur van Rootselaar Journal: Tremor Other Hyperkinet Mov (N Y) Date: 2018-01-23
Authors: Yongxing Zhou; Raman Sood; Qun Wang; Blake Carrington; Morgan Park; Alice C Young; Daniel Birnbaum; Zhao Liu; Tetsuo Ashizawa; James C Mullikin; Mohamad Z Koubeissi; Paul Liu Journal: Epilepsia Open Date: 2021-02-02