ClinVar

In an Italian father and 2 sons with peripheral neuropathy, Del Bo et al. (2008) identified a heterozygous c.310C-T transition in exon 4 of the MFN2 gene, resulting in an arg104-to-trp (R104W) substitution at a highly conserved residue in the GTPase domain. The phenotype was highly variable within the family. The father had a symmetric axonal, predominantly motor polyneuropathy, spastic gait, and pes cavus, consistent with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), as well as impaired nocturnal vision and sensorineural hearing loss, consistent with hereditary motor and sensory neuropathy type VIA (HMSN6A; 601152). He also showed cognitive decline first noted in his forties. Both sons had delayed motor and language development, decreased IQ, steppage gait, distal muscle weakness and atrophy, and axonal sensorimotor neuropathy at ages 10 and 7 years, respectively. One son also had optic nerve dysfunction. MR spectroscopy (MRS) in the father suggested a defect in mitochondrial energy metabolism in the occipital cortex. Del Bo et al. (2008) suggested that central nervous system involvement and cognitive impairment may be other phenotypic features of MFN2 mutations.