|MFN2 mutations cause severe phenotypes in most patients with CMT2A.|
|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|
|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-04-20|
|Title: Neurology Volume: 76 ISSN: 1526-632X ISO Abbreviation: Neurology Publication Date: 2011 May|
|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|
|Languages: eng Pagination: 1690-6 Citation Subset: AIM; IM|
|APA/MLA Format Download EndNote Download BibTex|
Aged, 80 and over
Charcot-Marie-Tooth Disease / genetics*
DNA / genetics
GTP Phosphohydrolases / genetics, metabolism
Magnetic Resonance Imaging
Membrane Proteins / genetics*
Mitochondrial Proteins / genetics*
Muscle Weakness / etiology, physiopathology
Muscle, Skeletal / physiopathology
Mutation / physiology*
Neural Conduction / physiology
Peripheral Nervous System Diseases / pathology
Reverse Transcriptase Polymerase Chain Reaction
|1U54NS065712-01/NS/NINDS NIH HHS; G0601943//Medical Research Council; //Department of Health; //Medical Research Council|
|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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