Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
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DOI：
10.1002/ana.20797
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发表时间：
2006-02-01
影响因子：
11.2
通讯作者：
Vance, JM
中科院分区：
文献类型：
--
作者：
Züchner, S;De Jonghe, P;Vance, JM
目的：Charcot-Marie-Tooth （CMT）神经病变伴视神经萎缩导致的视力损害被认定为遗传性运动和感觉神经病变VI型（HMSN VI）。受影响家庭的报告表明常染色体显性和隐性形式，但这种疾病的遗传原因仍然难以捉摸。方法：在这里，我们描述了6个HMSN VI家族，其中60%的患者出现亚急性视神经萎缩，随后视力恢复缓慢。进行了详细的临床和遗传学研究。结果。在每个谱系中，我们都发现了线粒体分裂蛋白2 （MFN2）基因的独特突变。在三个家族中，MFN2突变是从头发生的；在两个家庭中，突变随后从父亲传给儿子，表明常染色体显性遗传。解释：MFN2是一种线粒体膜蛋白，最近被报道引起2A型轴突CMT。有趣的是，MFN2显示出与视神经萎缩1 （OPA1）的功能重叠，OPA1是常染色体显性视神经萎缩最常见形式的蛋白，线粒体编码的氧化磷酸化成分见于Leber遗传性视神经萎缩。我们得出结论，常染色体显性HMSN VI是由MFN2突变引起的，强调了线粒体功能在视神经萎缩和周围神经病变中的重要作用。
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.