MFN2 mutations cause severe phenotypes in most patients with CMT2A

S. M. E FEELY; M LAURA; C. E SISKIND; S SOTTILE; M DAVIS; V. S GIBBONS; M. M REILLY; M. E SHY

doi:10.1212/WNL.0b013e31821a441e

Back

MFN2 mutations cause severe phenotypes in most patients with CMT2A

Journal article

Open access

Peer reviewed

MFN2 mutations cause severe phenotypes in most patients with CMT2A

S. M. E FEELY, M LAURA, C. E SISKIND, S SOTTILE, M DAVIS, V. S GIBBONS, M. M REILLY and M. E SHY

Neurology, Vol.76(20), pp.1690-1696

2011

DOI: 10.1212/WNL.0b013e31821a441e

PMCID: PMC3100135

PMID: 21508331

Files and links (1)

url

https://europepmc.org/articles/pmc3100135View

Published (Version of record) Open Access

Abstract

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.

Neurology

Biological and medical sciences

Medical sciences

Diseases of striated muscles. Neuromuscular diseases

Details

Title: Subtitle: MFN2 mutations cause severe phenotypes in most patients with CMT2A
Creators: S. M. E FEELY - Department of Neurology, Wayne State University, Detroit, MI, United States
M LAURA - MRC Centre for Neuromuscular Diseases Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom
C. E SISKIND - Department of Neurology, Wayne State University, Detroit, MI, United States
S SOTTILE - Department of Neurology, Wayne State University, Detroit, MI, United States
M DAVIS - University College London
V. S GIBBONS - MRC Centre for Neuromuscular Diseases Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom
M. M REILLY - MRC Centre for Neuromuscular Diseases Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom
M. E SHY - Department of Neurology, Wayne State University, Detroit, MI, United States
Resource Type: Journal article
Publication Details: Neurology, Vol.76(20), pp.1690-1696
DOI: 10.1212/WNL.0b013e31821a441e
PMID: 21508331
PMCID: PMC3100135
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: Lippincott Williams & Wilkins; Hagerstown, MD
Language: English
Date published: 2011
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984020655702771

Metrics

10 Record Views

169 Times Cited - Web of Science