MFN2 and Charcot-Marie-Tooth disease: Heterozygous MME variants have also been reported as a relatively common cause of milder, later-onset CMT with both reduced penetrance and semidominance.25, 28 However, the association of heterozygous MME variants with autosomal dominant CMT has been controversial,4 27 28 with suggestions that these variants do not cause disease, but are possibly risk alleles increasing susceptibility to disease.4 27 Reduced penetrance has also been reported for variants in more common IPN-associated genes, including PMP22 and MFN2.