MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2
MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2
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DOI：
10.1093/brain/awl126
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发表时间：
2006-08-01
期刊：
影响因子：
14.5
通讯作者：
Timmerman, Vincent
中科院分区：
文献类型：
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作者：
Verhoeven, Kristien;Claeys, Kristl G.;Timmerman, Vincent
已有报道在Charcot-Marie-Tooth Type 2(CMT2)家系中发现了丝裂原蛋白2(Mfn2)突变。为了研究Mfn2基因突变的分布，我们筛选了323个具有不同CMT表型的家系和孤立的患者。在29个先证者中，我们发现了22个不同的Mfn2突变，其中14个以前没有报道过。所有突变均位于Mfn2蛋白的细胞质区域。患者表现为典型但相当严重的CMT表型，因为28%的患者依赖轮椅。有些人还有其他特征，如视神经萎缩。大多数患者起病早，病情严重，而少数患者起病晚，病程较轻。电生理数据显示，大多数患者的神经传导速度正常至轻度降低，复合运动和感觉神经动作电位的波幅往往严重降低。对腓肠神经标本的检查显示大的有髓纤维丢失和线粒体变性改变。在有CMT2家族病史的患者中，Mfn2突变的频率为33%，这表明Mfn2突变是该人群的主要原因。
Mutations in mitofusin 2 (MFN2) have been reported in Charcot-Marie-Tooth type 2 (CMT2) families. To study the distribution of mutations in MFN2 we screened 323 families and isolated patients with distinct CMT phenotypes. In 29 probands, we identified 22 distinct MFN2 mutations, and 14 of these mutations have not been reported before. All mutations were located in the cytoplasmic domains of the MFN2 protein. Patients presented with a classical but rather severe CMT phenotype, since 28% of them were wheelchair-dependent. Some had additional features as optic atrophy. Most patients had an early onset and severe disease status, whereas a smaller group experienced a later onset and milder disease course. Electrophysiological data showed in the majority of patients normal to slightly reduced nerve conduction velocities with often severely reduced amplitudes of the compound motor and sensory nerve action potentials. Examination of sural nerve specimens showed loss of large myelinated fibres and degenerative mitochondrial changes. In patients with a documented family history of CMT2 the frequency of MFN2 mutations was 33% indicating that MFN2 mutations are a major cause in this population.