Mechanisms of disease and clinical features of mutations of the gene for mitofus

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Dev Med Child Neurol. 2010 Feb 12.

Mechanisms of disease and clinical features of mutations of the gene for

mitofusin 2: an important cause of hereditary peripheral neuropathy with

striking clinical variability in children and adults.

Ouvrier R, Grew S.

The Children's Hospital at Westmead, Westmead, NSW, Australia.

Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial

membrane, promotes membrane fusion and is involved in the maintenance of the

morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2

(MFN2) have recently been identified as the cause of approximately one-third of

dominantly inherited cases of the axonal degenerative forms of

Charcot-Marie-Tooth disease (CMT type 2A) and of rarer variants. The latter

include a severe, early-onset axonal neuropathy, which may occur in autosomal

dominant or recessive forms, as well as some instances associated with pyramidal

tract involvement (CMT type 5), with optic atrophy (CMT type 6), and,

occasionally, with alterations of cerebral white matter. All individuals with a

dominantly or recessively inherited or otherwise unexplained, chronic

progressive axonal degenerative polyneuropathy should be tested for mutations of

MFN2.