ClinVar

In a Korean mother and daughter with Charcot-Marie-Tooth disease-2A2A (CMT2A2A; 609260), Chung et al. (2006) identified a heterozygous 1085C-T transition in the MFN2 gene, resulting in a thr362-to-met (T362M) substitution. The patients had late onset and a mild phenotype.

In 2 adult Italian sibs with autosomal recessive inheritance of severe early-onset CMT2A2B (617087), Polke et al. (2011) identified compound heterozygosity for 2 mutations in the MFN2 gene: a T362M substitution on the maternal allele, and a 3-bp in-frame deletion (113delAGA; 608507.0020) resulting in a deletion of lys38 (lys38del), presumably from the paternal allele, although no DNA was available from the deceased father. The patients had onset of foot drop and upper and lower limb weakness at age 3 years. They also had decreased pinprick and vibration senses, more severe in the lower limbs, kyphosis, pale optic discs, visual loss, severe facial weakness, and respiratory muscle weakness. One had hearing loss and vocal cord palsy. Both were wheelchair-bound. Nerve conduction studies showed absence of nerve conduction in 1 patient tested. Neither parent was affected. Polke et al. (2011) noted that the T362M mutation had also been reported in families with dominant transmission, suggesting that it has a dominant-negative effect; the pathogenic effect of the lys38 deletion mutation was unknown, although it was not found in 550 control chromosomes.

In a 32-year-old woman (CMT742) with autosomal recessive CMT2A2B, Nicholson et al. (2008) identified compound heterozygosity for 2 missense mutations in the MFN2 gene: T362M and A164V (608507.0021).