Journal article
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
Annals of neurology, Vol.59(2), pp.276-281
2006
DOI: 10.1002/ana.20797
PMID: 16437557
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 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.
Details
- Title: Subtitle
- Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
- Creators
- Stephan ZÜCHNER - Center for Human Genetics, and Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United StatesPeter DE JONGHE - Molecular Genetics Department, Flanders Interuniversiry Institute for Biotechnology, University of Antwerp, BelgiumIvajlo TOURNEV - Department of Neurology, Sofia Medical University, Sofia, BulgariaKristien VERHOEVEN - Molecular Genetics Department, Flanders Interuniversiry Institute for Biotechnology, University of Antwerp, BelgiumChristine T LANGERHORST - Department of Ophthalmology, Academic Medical Center, Amsterdam, NetherlandsMarianne DE VISSER - Department of Neurology, Academic Medical Center, Amsterdam, NetherlandsFrank BAAS - Department of Neurology, Academic Medical Center, Amsterdam, NetherlandsThomas BIRD - Department of Neurology, University of Washington, Geriatric Research Center, VA Medical Center, Seattle, WA, United StatesVincent TIMMERMAN - Molecular Genetics Department, Flanders Interuniversiry Institute for Biotechnology, University of Antwerp, BelgiumMichael SHY - Department of Neurology, Wayne State University School of Medicine, Detroit, MI, United StatesJeffery M VANCE - Center for Human Genetics, and Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United StatesAlbena JORDANOVA - Molecular Genetics Department, Flanders Interuniversiry Institute for Biotechnology, University of Antwerp, BelgiumKristl G CLAEYS - Molecular Genetics Department, Flanders Interuniversiry Institute for Biotechnology, University of Antwerp, BelgiumVelina GUERGUELTCHEVA - Department of Neurology, Sofia Medical University, Sofia, BulgariaSylvia CHERNINKOVA - Department of Neurology, Sofia Medical University, Sofia, BulgariaSteven R HAMILTON - Neuroophthalmology Unit, Neuroscience Institute, Swedish Medical Center, Seattle, WA, United StatesGreg VAN STAVERN - Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI, United StatesKaren M KRAJEWSKI - Department of Neurology, Wayne State University School of Medicine, Detroit, MI, United StatesJeffery STAJICH - Center for Human Genetics, and Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.59(2), pp.276-281
- Publisher
- Willey-Liss; Hoboken
- DOI
- 10.1002/ana.20797
- PMID
- 16437557
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Grant note
- name: CMT families; name: NIH, award: NS26630; name: NINDS grants; name: Fund for Scientific Research-Flanders; name: Medical Foundation Queen Elisabeth; DOI: 10.13039/501100007660, name: University of Antwerp; name: Interuniversity Attraction Poles program of the Belgian Federal Science Office; DOI: 10.13039/501100001826, name: Netherlands Organization for Health Research and Development; name: VA Research Funds; name: Visiting research fellowships from the POD; name: NATO/FWO. a postdoctoral fellow of the FWO, Belgium
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984014345002771
Metrics
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