Mutation screening of mitofusin 2 in CMT 2A

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J Neurol. 2011 Jan 22. [Epub ahead of print]

Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2.

McCorquodale DS 3rd, Montenegro G, Peguero A, Carlson N, Speziani F, Price J,

SW, Melanson M, Vance JM, Züchner S.

Department of Human Genetics, P. Hussman Institute for Human Genomics,

University of Miami School of Medicine, Biomedical Research Building,

Room 523, LC: M-860, 1501 NW 10th Avenue, Miami, FL, 33136, USA.

Abstract

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.