Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

S Züchner, P De Jonghe, A Jordanova… - Annals of Neurology …, 2006 - Wiley Online Library
S Züchner, P De Jonghe, A Jordanova, KG Claeys, V Guergueltcheva, S Cherninkova…
Annals of Neurology: Official Journal of the American Neurological …, 2006Wiley Online Library
Abstract 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 …
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
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