Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2.
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.
Department of Human Genetics, John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Biomedical Research Building, Room 523, LC: M-860, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Donald S
DS
McCorquodale
Gladys
G
Montenegro
Ainsley
A
Peguero
Nicole
N
Carlson
Fiorella
F
Speziani
Justin
J
Price
Sean W
SW
Taylor
Michel
M
Melanson
Jeffery M
JM
Vance
Stephan
S
Züchner
D000293:Adolescent; D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020558:GTP Phosphohydrolases; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D055815:Young Adult
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
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