Analysis of the clinical phenotypes of Charcot-Marie-Tooth disease type 2A2 patients with mitofusin2 mutation

Objective: To investigate the characteristics of mitofusin2 (MFN2) mutation and the clinical variability of Charcot-Marie-Tooth disease type 2 (CMT2) patients. Methods: MFN2 mutation analysis were performed in 8 autosomal dominant CMT2 families and 24 sporadic CMT2 cases by PCR and direct sequencing. The clinical features of the positive cases were precisely analyzed. Results: Sequencing of the MFN2 gene revealed 4 different missense mutations, and detection rate was 4 of 32 (12.5%) in patients with CMT2. c. 281G≤A (R94Q) and c. 2240 T≤C (M747T) were detected in 2 autosomal dominant pedigrees, and intrafamilial clinical phenotype variability was present; c. 1090 C≤T (R364W)and c. 2198 T≤C (1.733P) were detected in 2 sporadic cases, and the latter was a novel mutation which had not been reported. In addition to weakness and atrophy in the distal limbs, the former sporadic case was optic atrophy, and the latter case was hyperkeratosis of the skin. Conclusions: Divergent MFN2 mutations are frequently found among axonal varieties of CMT2 in the Chinese population, and analysis of phenotypes in the CMT2A2 patients indicate the high clinical variability of this disease.