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Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
Author(s) -
Züchner Stephan,
De Jonghe Peter,
Jordanova Albena,
Claeys Kristl G.,
Guergueltcheva Velina,
Cherninkova Sylvia,
Hamilton Steven R.,
Van Stavern Greg,
Krajewski Karen M.,
Stajich Jeffery,
Tournev Ivajlo,
Verhoeven Kristien,
Langerhorst Christine T.,
de Visser Marianne,
Baas Frank,
Bird Thomas,
Timmerman Vincent,
Shy Michael,
Vance Jeffery M.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20797
Subject(s) - mfn2 , atrophy , optic neuropathy , mutation , pathology , mitochondrial disease , biology , mitochondrial dna , medicine , genetics , optic nerve , anatomy , mitochondrial fusion , gene
Objective Charcot‐Marie‐Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive. Methods Here, we describe six HMSN VI families with a subacute onset of optic atrophy and subsequent slow recovery of visual acuity in 60% of the patients. Detailed clinical and genetic studies were performed. Results In each pedigree, we identified a unique mutation in the gene mitofusin 2 ( MFN2 ). In three families, the MFN2 mutation occurred de novo; in two families the mutation was subsequently transmitted from father to son indicating autosomal dominant inheritance. Interpretation MFN2 is a mitochondrial membrane protein that was recently reported to cause axonal CMT type 2A. It is intriguing that MFN2 shows functional overlap with optic atrophy 1 (OPA1), the protein underlying the most common form of autosomal dominant optic atrophy, and mitochondrial encoded oxidative phosphorylation components as seen in Leber's hereditary optic atrophy. We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2 , emphasizing the important role of mitochondrial function for both optic atrophies and peripheral neuropathies. Ann Neurol 2006;59:276–281