Background: Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2.
Methods: Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene.
Results: We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4% (8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes.
Conclusions: The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2.