Mitofusin 2 gene mutation causing early-onset CMT2A with different progressive courses

• Published in: Clinical neuropathology Vol. 32; no. 1; p. 16
• Main Authors: Lv, He, Wang, Lu, Li, Wurong, Qiao, Xiaohui, Li, Yuexing, Wang, Zhaoxia, Yuan, Yun
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2013
• Subjects: Adolescent; Adult; Age of Onset; Base Sequence; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - pathology; Charcot-Marie-Tooth Disease - physiopathology; Child; Child, Preschool; Disease Progression; Female; Genotype; GTP Phosphohydrolases - genetics; Humans; Male; Middle Aged; Mitochondrial Proteins - genetics; Molecular Sequence Data; Mutation; Pedigree; Phenotype; Young Adult
• ISSN: 0722-5091
• DOI: 10.5414/NP300464

Charcot-Marie-Tooth disease Type 2A2 (CMT2A2), caused by mitofusin 2 (MFN2) genes, has been clinically classified into two types: severe early-onset and mild benign. Here we reported 3 early onset patients with different progressive courses. The 3 patients had mutations R94W, R364W and a novel W740R in the MFN2 gene. Two patients presented with progressive distal limb muscle weakness and wasting from the ages of 5 and 6 years, respectively. The disease developed slowly, with loss of ambulation after 35 years of age. The third patient presented with similar symptoms after birth, and has never been able to walk independently. Sural nerve biopsies revealed severe axonal neuropathy with mitochondrial aggregation in axons. Our data confirmed that early-onset CMT2A2 can present with different courses in Chinese patients. The novel mutation in MFN2 found in this study broadens the genotypic spectrum associated with MFN2 related CMT.