Department of Neurology, Wayne State University, 421 Ea Canfield, Detroit, MI 48201, USA.
Neurology. 2011 May 17;76(20):1690-6. doi: 10.1212/WNL.0b013e31821a441e. Epub 2011 Apr 20.
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common form of CMT2, is caused by mutations in the mitofusin 2 gene (MFN2), a nuclear encoded gene essential for mitochondrial fusion and tethering the endoplasmic reticulum to mitochondria. Published CMT2A phenotypes have differed widely in severity.
To determine the prevalence and phenotypes of CMT2A within our clinics we performed genetic testing on 99 patients with CMT2 evaluated at Wayne State University in Detroit and on 27 patients with CMT2 evaluated in the National Hospital for Neurology and Neurosurgery in London. We then preformed a cross-sectional analysis on our patients with CMT2A.
Twenty-one percent of patients had MFN2 mutations. Most of 27 patients evaluated with CMT2A had an earlier onset and more severe impairment than patients without CMT2A. CMT2A accounted for 91% of all our severely impaired patients with CMT2 but only 11% of mildly or moderately impaired patients. Twenty-three of 27 patients with CMT2A were nonambulatory prior to age 20 whereas just one of 78 non-CMT2A patients was nonambulatory after this age. Eleven patients with CMT2A had a pure motor neuropathy while another 5 also had profound proprioception loss. MFN2 mutations were in the GTPase domain, the coiled-coil domains, or the highly conserved R3 domain of the protein.
We find MFN2 mutations particularly likely to cause severe neuropathy that may be primarily motor or motor accompanied by prominent proprioception loss. Disruption of functional domains of the protein was particularly likely to cause neuropathy.
Charcot-Marie-Tooth 病型 2A（CMT2A）是最常见的 CMT2 类型，由线粒体融合蛋白 2 基因（MFN2）的突变引起，该基因为核编码基因，对线粒体融合和将内质网与线粒体连接至关重要。已发表的 CMT2A 表型在严重程度上差异很大。
为了确定我们诊所中 CMT2A 的患病率和表型，我们对在底特律韦恩州立大学评估的 99 例 CMT2 患者和在伦敦国家神经病学和神经外科学院评估的 27 例 CMT2 患者进行了基因检测。然后，我们对我们的 CMT2A 患者进行了横断面分析。
21%的患者存在 MFN2 突变。与没有 CMT2A 的患者相比，评估的 27 例 CMT2A 患者大多数发病较早，病情较重。CMT2A 占我们所有严重受损的 CMT2 患者的 91%，但仅占轻度或中度受损患者的 11%。27 例 CMT2A 患者中有 23 例在 20 岁之前无法行走，而 78 例非 CMT2A 患者中只有 1 例在这个年龄之后无法行走。11 例 CMT2A 患者患有纯运动神经病，另有 5 例患者还伴有严重的本体感觉丧失。MFN2 突变位于 GTPase 结构域、卷曲螺旋结构域或该蛋白高度保守的 R3 结构域。
我们发现 MFN2 突变特别可能导致严重的神经病变，可能主要是运动性的或伴有明显的本体感觉丧失。该蛋白功能域的破坏特别可能导致神经病变。
