Charcot-Marie-Tooth disease (CMT)

Charcot-Marie-Tooth disease is the most common inherited disease affecting peripheral nerves in humans. Symptoms can vary even within families, and the disability experienced can range from mild to severe. As evidence mounts for the genetic basis of the disorder's different forms, scientists can begin to develop therapies to specifically target the root causes of CMT in particular families.

Drs. Jeffery Vance and Kamel Ben Othmane initially localized the CMT2A locus to chromosome 1p35-36 in 1993. After additional further research narrowed the region containing the gene, Zhao et al. reported a missense change in KIFIB, but it was in a single small pedigree with CMT2A. Since no further mutations could be found in KIFIB in the multiple CMT2A families studied worldwide, we searched for another gene that was the cause for the majority of CMT2A cases. After screening 15 genes, MIHG faculty members Dr. Stephan Züchner and Dr. Jeffery Vance with other colleagues found mutations in the Mitofusin 2 gene in all known families linked to the CMT2A locus (families in USA, Italy, Japan, Turkey and Russia). MIHG researchers found MFN2 mutations in about 20% of our 36 CMT2 isolated patients. Recently, the Department of Molecular Genetics Lab, University of Antwerp, Belgium, found about 10% of their 140 families had MFN2 mutations. This finding makes MFN2 by far the most important CMT2 gene found to date.