Department of Neurology, Ewha Womans University, School of Medicine, Seoul, Korea.
Hum Mutat. 2012 Nov;33(11):1610-5. doi: 10.1002/humu.22143. Epub 2012 Jul 5.
Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is a genetically and clinically heterogeneous disorder with variable inheritance modes. As several molecules have been reported to have therapeutic effects on CMT, depending on the underlying genetic causes, exact genetic diagnostics have become very important for executing personalized therapy. Whole-exome sequencing has recently been introduced as an available method to identify rare or novel genetic defects from genetic disorders. Particularly, CMT is a model disease to apply exome sequencing because more than 50 genes (loci) are involved in its development with weak genotype-phenotype correlation. This study performed the exome sequencing in 25 unrelated CMT patients who revealed neither 17p12 duplication/deletion nor several major CMT genes. This study identified eight causative heterozygous mutations (32%). This detection rate seems rather high because each sample was tested before the study for major genetic causes. Therefore, this study suggests that the exome sequencing can be a highly exact, rapid, and economical molecular diagnostic tool for CMT patients who are tested for major genetic causes.
腓骨肌萎缩症（CMT）是最常见的遗传性周围神经病之一，是一种遗传和临床异质性疾病，具有不同的遗传模式。由于已有几种分子被报道对 CMT 具有治疗作用，具体取决于潜在的遗传原因，因此明确的遗传诊断对于执行个体化治疗变得非常重要。外显子组测序最近已被引入作为一种从遗传疾病中识别罕见或新的遗传缺陷的可用方法。特别是 CMT 是应用外显子组测序的模型疾病，因为有 50 多个基因（基因座）参与其发展，其基因型与表型相关性较弱。本研究对 25 名无 17p12 重复/缺失且无几种主要 CMT 基因的无关 CMT 患者进行了外显子组测序。本研究鉴定出 8 个致病性杂合突变（32%）。由于在研究前每个样本均针对主要遗传原因进行了检测，因此该检测率似乎相当高。因此，本研究表明，外显子组测序可以作为一种高度准确、快速且经济的分子诊断工具，用于检测主要遗传原因的 CMT 患者。
