title: MFN2-related genetic and clinical features in a cohort of Chinese CMT2 patients.
abstract: Charcot-Marie-Tooth disease 2A (CMT2A), caused by mutations in the mitofusin 2 gene (MFN2), is the most common CMT2 subtype. The aim of our study is to assess the frequency and summarize the genetic and clinical characteristics of Chinese CMT2A patients. A total of 17 coding exons of MFN2 were detected by direct sequencing in 82 unrelated Chinese families diagnosed as CMT2. Clinical evaluations were analyzed among CMT2A patients. We identified 14 missense variants in 9 sporadic and 6 familial cases, including four novel mutations (T129A, S249F, Q367P, and Q674L), 4 known mutations (R94W, R94Q, T105M, C132Y, M376V and Q751X), and 4 rare missense variants (K120E, C217F, K307E and T356S). A total of 23 patients had early-onset phenotype. Two patients had a CMTNS score of 0 to 10; 16 had a score of 11 to 20; and 7 had a score greater than 20. Five patients were confirmed a de novo origin. Six of 14 variants were located or closed to the GTPase domain. We report four novel mutations and four rare missense variants. MFN2 mutations account for 18% of CMT2 families in mainland China. The common characteristics of Chinese pedigree are early disease onset and moderate phenotypes.
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: National Key Lab of Medical Genetics, Central South University, Changsha, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Yajin
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zi
authors.affiliation: National Key Lab of Medical Genetics, Central South University, Changsha, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: National Key Lab of Medical Genetics, Central South University, Changsha, China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, the Third Xiangya Hospital, Changsha, China.
authors.forename: Ruxu
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: CMT2A; Charcot-Marie-Tooth disease; MFN2; clinical features; mutational rate