Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations
Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations
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DOI：
10.1093/brain/awl174
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发表时间：
2006-08-01
期刊：
影响因子：
14.5
通讯作者：
Choi, B. O.
中科院分区：
文献类型：
--
作者：
Chung, K. W.;Kim, S. B.;Choi, B. O.
线粒体融合蛋白2（MFN 2）基因（其编码线粒体GTP酶线粒体融合蛋白）中的突变最近已被报道引起Charcot-Marie-Tooth 2A（CMT 2A）和遗传性运动和感觉神经病VI（HMSN VI）。众所周知，HMSN VI是一种伴有视神经萎缩的轴突CMT神经病。然而，CMT 2A和具有MFN 2突变的HMSN VI之间的差异仍有待澄清。因此，我们研究了MFN 2突变的CMT患者的表型特征。在62个无关的轴突型CMT神经病家族中筛选MFN 2突变。我们计算CMT神经病变评分（CMTNS）和功能障碍量表（FDS），以量化疾病的严重程度。通过脑MRI研究了21例MFN 2突变患者。在15个家系的26例患者中发现了10种致病性突变（24.2%）。这些突变中有6个尚未报道，在5个家族（33.3%）中观察到新发突变。MFN 2突变患者的电生理模式是典型的轴突CMT;然而，早期（< 10年）和晚期发病（>= 10年）组的临床和电生理特征明显不同。所有早发患者均患有重度CMTNS（>= 21）和FDS（6或7），而大多数迟发患者患有轻度CMTNS（
Mutations in the mitofusin 2 (MFN2) gene, which encodes a mitochondrial GTPase mitofusin protein, have recently been reported to cause both Charcot-Marie-Tooth 2A (CMT2A) and hereditary motor and sensory neuropathy VI (HMSN VI). It is well known that HMSN VI is an axonal CMT neuropathy with optic atrophy. However, the differences between CMT2A and HMSN VI with MFN2 mutations remained to be clarified. Therefore, we studied the phenotypic characteristics of CMT patients with MFN2 mutations. Mutations in MFN2 were screened in 62 unrelated axonal CMT neuropathy families. We calculated CMT neuropathy scores (CMTNSs) and functional disability scales (FDSs) to quantify disease severity. Twenty-one patients with the MFN2 mutations were studied by brain MRI. Ten pathogenic mutations were identified in 26 patients from 15 families (24.2%). Six of these mutations had not been reported, and de novo mutations were observed in five families (33.3%). The electrophysiological patterns of affected individuals with the MFN2 mutations were typical of axonal CMT; however, the clinical and electrophysiological characteristics were markedly different in early (< 10 years) and late disease-onset (>= 10 years) groups. All patients with an early onset had severe CMTNS (>= 21) and FDS (6 or 7), whereas most patients with late onset had mild CMTNS (