We found a novel MFN2 mutation - c.283A>G (p.Arg95Gly) - that results in an axonal neuropathy with variable clinical severity in a multigenerational family.
MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth.
We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2.
A cohort of 139 unrelated Czech patients with axonal neuropathy was selected for sequencing and multiplex ligation-dependent probe amplification analysis (MLPA) testing of the MFN2 gene.
In small kindreds, specific MFN2 mutations have been reported to associate with severity of axonal neuropathy, optic atrophy, and involvement of the central nervous system.
Molecular analysis aimed at detecting mutations of MFN2 could be extremely useful in mild axonal neuropathies with slow evolution and indispensable in cases of dominant inheritance or optic atrophy.
The aim of this study was to investigate the mode of inheritance in three individuals with severe early-onset axonal neuropathy and homozygous or compound heterozygous MFN2 mutations.
Our results suggest that the sharply reduced efficacy of oxidative phosphorylation in MFN2-related CMT2A may contribute to the pathophysiology of the axonal neuropathy.