Simultaneous MFN2 and GDAP1 mutations cause major mitochondrial defects in a patient with CMT

Abstract

Mutations in the MFN2 gene are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a dominant axonal CMT, whereas mutations in GDAP1 are associated with recessive demyelinating CMT (CMT4A), recessive axonal CMT (AR-CMT2), and dominant axonal CMT (CMT2K). Both proteins are involved in energy metabolism and dynamics of the mitochondrial network. We have previously reported that, in fibroblasts from patients with CMT, MFN2 mutations resulted in a mitochondrial energy coupling defect, whereas dominant mutation in GDAP1 resulted in defective complex I activity. In this study, we investigated mitochondrial bioenergetics from a severely affected patient with CMT harboring combined mutations in both GDAP1 and MFN2 genes.