title: A cohort study of Han Chinese MFN2-related Charcot-Marie-Tooth 2A.
abstract: BACKGROUND
  Charcot-Marie-Tooth 2A (CMT2A) is caused by mutations in mitochondrial fusion protein mitofusin 2 (MFN2). CMT2A had a large variety of clinical symptoms and several cohort studies were published recently. This study is to summarized the clinical, electrophysiological, pathological and genetic features in Han Chinese CMT2A.
  
  
  METHODS
  20 patients from 12 unrelated Chinese families with MFN2 related CMT2A were collected. Clinical symptom, nerve conduction velocity study, sural nerve pathology and MFN2 gene mutation were retrospectively analyzed.
  
  
  RESULTS
  We confirmed MFN2 gene mutation in 12 indexes. Nineteen of 20 (95%) patients were classified as early onset phenotypes of CMT2A, including four cases (20%) with infantile onset. Motor nerve conduction velocity (MNCV) of median nerve was above 38m/s in 50% of patients and not recordable in remaining patients. MNCV was not affected by onset age, disease course and mutation site in different patients and MNCV had no correlation with severity of symptoms. Sural nerve biopsy revealed mixed axonal and demyelination change. Loss of myelinated fibers and atypical onions was found in all cases. Electron microscopic (EM) examination of sural nerve confirmed mitochondrial vacuation and aggregation both in myelinated and unmyelinated axons. Eight mutations were detected in 12 indexes, including two novel mutations. The amino acid residue at position 94 of MFN2 protein was a hot spot in Han Chinese patients, followed by R104W.
  
  
  CONCLUSIONS
  Eraly onset, even infantile onset was more common in our Chinese population. MNCV of median nerve could be either above 38m/s or unrecordable in CMT2A. Pathologically, mixed axon and myelin change should be considered since onion change was frequently observed in most CMT2A.
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Lv
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: Yuehuan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, First Hospital, Peking University, Beijing 100034, PR China. Electronic address: yuanyun2002@126.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D009431:Neural Conduction / Q000502:physiology*; D010641:Phenotype; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: Axonal neuropathy; Charcot–Maria–Tooth; Early onset; Hereditary neuropathy; Mitofusin 2; Pathology