MFN2‐related genetic and clinical features in a cohort of Chinese CMT2 patients

Charcot‐Marie‐Tooth disease 2A ( CMT2A ), caused by mutations in the mitofusin 2 gene ( MFN2 ), is the most common CMT2 subtype. The aim of our study is to assess the frequency and summarize the genetic and clinical characteristics of Chinese CMT2A patients. A total of 17 coding exons of MFN2 were detected by direct sequencing in 82 unrelated Chinese families diagnosed as CMT2 . Clinical evaluations were analyzed among CMT2A patients. We identified 14 missense variants in 9 sporadic and 6 familial cases, including four novel mutations ( T129A , S249F , Q367P , and Q674L ), 4 known mutations ( R94W , R94Q , T105M , C132Y , M376V and Q751X ), and 4 rare missense variants ( K120E , C217F , K307E and T356S ). A total of 23 patients had early‐onset phenotype. Two patients had a CMTNS score of 0 to 10; 16 had a score of 11 to 20; and 7 had a score greater than 20. Five patients were confirmed a de novo origin. Six of 14 variants were located or closed to the GTPase domain. We report four novel mutations and four rare missense variants. MFN2 mutations account for 18% of CMT2 families in mainland China. The common characteristics of Chinese pedigree are early disease onset and moderate phenotypes.