MFN2 mutations cause severe phenotypes in most patients with CMT2A

• DOI: 10.1212/wnl.0b013e31821a441e
• Publication Date: 2011-04-21T04:40:23Z
• Authors: S.M.E. Feely; M. Laura; C.E. Siskind; S. Sottile; M. Davis; V.S. Gibbons; M.M. Reilly; M.E. Shy
• Keywords: MFN2

Charcot-Marie-Tooth disease type 2A (CMT2A), the most common form of CMT2, is caused by mutations in mitofusin 2 gene (MFN2), a nuclear encoded essential for mitochondrial fusion and tethering endoplasmic reticulum to mitochondria. Published CMT2A phenotypes have differed widely severity.To determine prevalence within our clinics we performed genetic testing on 99 patients with CMT2 evaluated at Wayne State University Detroit 27 National Hospital Neurology Neurosurgery London. We then preformed cross-sectional analysis CMT2A.Twenty-one percent had MFN2 mutations. Most an earlier onset more severe impairment than without CMT2A. accounted 91% all severely impaired but only 11% mildly or moderately patients. Twenty-three were nonambulatory prior age 20 whereas just one 78 non-CMT2A was after this age. Eleven pure motor neuropathy while another 5 also profound proprioception loss. GTPase domain, coiled-coil domains, highly conserved R3 domain protein.We find particularly likely cause that may be primarily accompanied prominent Disruption functional domains protein neuropathy.