Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2
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Charcot-Marie-Tooth (CMT) disease is among the most common inherited neurological disorders. Mutations in the gene mitofusin 2 (MFN2) cause the axonal subtype CMT2A, which has also been shown to be associated with optic atrophy, clinical signs of first motor neuron involvement, and early onset stroke. Mutations in MFN2 account for up to 20–30% of all axonal CMT type 2 cases. To further investigate the prevalence of MFN2 mutations and to add to the genotypic spectrum, we sequenced all exons of MFN2 in a cohort of 39 CMT2 patients. We identified seven variants, four of which are novel. One previously described change was co-inherited with a PMP22 duplication, which itself causes the demyelinating form CMT1A. Another mutation was a novel in frame deletion, which is a rare occurrence in the genotypic spectrum of MFN2 characterized mainly by missense mutations. Our results confirm a MFN2 mutation rate of ~15–20% in CMT2.
KeywordsCharcot-Marie-Tooth disease CMT2 CMT2A Mitofusin 2 MFN2 Inherited peripheral neuropathies
The participation of the patients and families in this study is gratefully acknowledged. The study was supported by grants by the Charcot-Marie-Tooth Association (to S.Z.) and the National Institute of Neurological Disorders and Stroke (to S.Z., R01NS052767).
Conflict of interest
Drs. Vance and Züchner are part of a license agreement with Athena Diagnostics Inc.
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