title: Fine mapping and whole-exome sequencing of a familial cortical myoclonic tremor with epilepsy family.
abstract: Familial cortical myoclonic tremor with epilepsy (FCMTE) is an autosomal dominant epilepsy syndrome. Four loci, including 8q24 (FCMTE1), 2p11.1-q12.2 (FCMTE2), 5p15.31-p15.1 (FCMTE3), and 3q26.32-3q28 (FCMTE4) were previously reported. Herein, we report a new FCMTE1 pedigree from Chinese population with its clinical and genetic study results. Whole genome scan was performed to identify the causative gene region and copy number variants. Whole-exome sequencing was used to identify the causative gene. There were twelve affected members alive in this FCMTE1 pedigree. Nine affected members had both cortical myoclonic tremor and epilepsy, while three affected members had only cortical myoclonic tremor. Electrophysiologic examinations manifested giant somatosensory evoked potentials and long-latency cortical reflex in some affected members. Whole genome scan identified a 20.4 Mb causative gene region at 8q22.3-q24.13. No copy number variants were identified as the causative mutation. Whole-exome sequencing identified a co-segregated mutation (c.206A>T; p.Y69F) in the SLC30A8 gene. However, the evidence supporting this gene as the causative gene of FCMTE1 is not enough. We report the first Chinese FCMTE1 pedigree. No copy number variants, point mutation or small insertion/deletion were detected in the identified region that showed an association with FCMTE1. Further studies could focus on other possible genetic mechanisms while the association between the SLC30A8 and FCMTE1 needs further evidence.
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Department of Pediatrics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Cen
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Dan-Ning
authors.initials: DN
authors.lastname: Lou
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xing-Jiao
authors.initials: XJ
authors.lastname: Lu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Ouyang
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Cheng du, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hou-Min
authors.initials: HM
authors.lastname: Yin
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhong-Jin
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D056915:DNA Copy Number Variations; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D020329:Essential Tremor / Q000235:genetics*; D059472:Exome; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017422:Sequence Analysis, DNA; D055815:Young Adult
keywords: familial cortical myoclonic tremor with epilepsy; whole genome scan; whole-exome sequencing