MFN2 point mutations occur in .3.5% of Charcot-Marie-Tooth families

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(Oral presentation at the Antwerp Consortium July 2009)

MFN2 point mutations occur in .3.5% of Charcot-Marie-Tooth families.

An investigation of 227 Norwegian CMT

G..T. Braathen1,2,3,4,.T. Christensen Sand4, A. Lobato4

, H. H~yer3 and M.B. RusseU1 ,2,4

Faculty Division Akershus University Hospital, University of Oslo, Oslo, Norway;

'Department of Neurology, Akershus University Hospital, Oslo, Norway;

'Department of Laboratory Medicine, Ielemark Hospital, Skien, Norway; 4Research

Centre, Akershus University Hospital, Oslo, Norway

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

intelmediate CMT. MFN2 point mutations are probably the most common cause of

CMT2.

Methods.. Two-hundred and thitty-five Norwegian CMT families were screened for

point mutations in the MFN2 gene.

Findings.. We identified 7 point mutations in 8 umelated CMT families Four

mutations were known, while three novel point mutations were not found in 100

healthy controls. This corresponds to 35% (8/227) of CMT families have point

mutations in the MFN2 gene.The phenotypes were compatible with CMT l in three

families, CMT 2 in three families, CMT

intermediate in one family and distal Hereditary Motor Neuropathy (dHMN) in one

family.

The point mutations were located in exon 4, 14, 15 and 18.

Intelpretation. The identified known and novel point mutations in the MFN2 gene

expand the clinical spectrum from CMT2 and CMT intermediate to also include CMTI

and the dHMN phenotypes. The mutation that caused the dHMN phenotype is the

fitst identified point mutation that does not affect the N- or the C-telminal of

the MFN2 protein.