Mitochondrial GTPase mitofusin 2 mutation in CMT 2A

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Abstract from Human Genetics. 2004 Nov 11

Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth

neuropathy type 2A.

Kijima K, Numakura C, Izumino H, Umetsu K, Nezu A, Shiiki T, Ogawa M,

Ishizaki Y, Kitamura T, Shozawa Y, Hayasaka K.

Department of Pediatrics, Yamagata University School of Medicine, 2-2-2

Iida-nishi, 990-9585, Yamagata, Japan.

Charcot-Marie-Tooth disease (CMT) has been classified into two types,

CMT1 and CMT2, demyelinating and axonal forms, respectively. CMT2 has

been further subdivided into eight groups by linkage studies. CMT2A is

linked to chromosome 1p35-p36 and mutation in the kinesin family member

1B-ss ( KIF1B) gene had been reported in one pedigree.

However, no mutation in KIF1B was detected in other pedigrees with CMT2A

and the mutations in the mitochondrial fusion protein mitofusin 2 (

MFN2) gene were recently detected in those pedigrees. MFN2, a

mitochondrial transmembrane GTPase, regulates the mitochondrial network

architecture by fusion of mitochondria. We studied MFN2 in 81 Japanese

patients with axonal or unclassified CMT and detected seven mutations in

seven unrelated patients. Six of them were novel and one of them was a

de novo mutation. Most mutations locate within or immediately upstream

of the GTPase domain or within two coiled-coil domains, which are

critical for the functioning or mitochondrial targeting of MFN2.

Formation of a mitochondrial network would be required to maintain the

functional peripheral nerve axon.