Document Detail

MFN2 mutations cause severe phenotypes in most patients with CMT2A.
MedLine Citation:
PMID:  21508331     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Charcot-Marie-Tooth disease type 2A (CMT2A), the most common form of CMT2, is caused by mutations in the mitofusin 2 gene (MFN2), a nuclear encoded gene essential for mitochondrial fusion and tethering the endoplasmic reticulum to mitochondria. Published CMT2A phenotypes have differed widely in severity.
METHODS: To determine the prevalence and phenotypes of CMT2A within our clinics we performed genetic testing on 99 patients with CMT2 evaluated at Wayne State University in Detroit and on 27 patients with CMT2 evaluated in the National Hospital for Neurology and Neurosurgery in London. We then preformed a cross-sectional analysis on our patients with CMT2A.
RESULTS: Twenty-one percent of patients had MFN2 mutations. Most of 27 patients evaluated with CMT2A had an earlier onset and more severe impairment than patients without CMT2A. CMT2A accounted for 91% of all our severely impaired patients with CMT2 but only 11% of mildly or moderately impaired patients. Twenty-three of 27 patients with CMT2A were nonambulatory prior to age 20 whereas just one of 78 non-CMT2A patients was nonambulatory after this age. Eleven patients with CMT2A had a pure motor neuropathy while another 5 also had profound proprioception loss. MFN2 mutations were in the GTPase domain, the coiled-coil domains, or the highly conserved R3 domain of the protein.
CONCLUSIONS: We find MFN2 mutations particularly likely to cause severe neuropathy that may be primarily motor or motor accompanied by prominent proprioception loss. Disruption of functional domains of the protein was particularly likely to cause neuropathy.
S M E Feely; M Laura; C E Siskind; S Sottile; M Davis; V S Gibbons; M M Reilly; M E Shy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-20
Journal Detail:
Title:  Neurology     Volume:  76     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-17     Completed Date:  2011-07-12     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1690-6     Citation Subset:  AIM; IM    
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MeSH Terms
Action Potentials / physiology
Aged, 80 and over
Charcot-Marie-Tooth Disease / genetics*
Child, Preschool
Cohort Studies
DNA / genetics
Electrophysiological Phenomena
GTP Phosphohydrolases / genetics,  metabolism
Magnetic Resonance Imaging
Membrane Proteins / genetics*
Middle Aged
Mitochondrial Proteins / genetics*
Muscle Weakness / etiology,  physiopathology
Muscle, Skeletal / physiopathology
Mutation / physiology*
Neural Conduction / physiology
Neurologic Examination
Peripheral Nervous System Diseases / pathology
Reverse Transcriptase Polymerase Chain Reaction
Young Adult
Grant Support
1U54NS065712-01/NS/NINDS NIH HHS; G0601943//Medical Research Council; //Department of Health; //Medical Research Council
Reg. No./Substance:
0/Membrane Proteins; 0/Mitochondrial Proteins; 9007-49-2/DNA; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/MFN2 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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