Miressi Federica, Magdelaine Corinne, Cintas Pascal, Bourthoumieux Sylvie, Nizou Angélique, Derouault Paco, Favreau Frédéric, Sturtz Franck, Faye Pierre-Antoine, Lia Anne-Sophie
Maintenance Myélinique et Neuropathies Périphériques, Université de Limoges, EA 6309, F-87000 Limoges, France.
Service de Biochimie et Génétique Moléculaire, Centre Hospitalier Universitaire à Limoges, F-87000 Limoges, France.
Brain Sci. 2020 Dec 15;10(12):986. doi: 10.3390/brainsci10120986.
Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited disorders affecting the peripheral nervous system, with a prevalence of 1/2500. So far, mutations in more than 80 genes have been identified causing either demyelinating forms (CMT1) or axonal forms (CMT2). Consequentially, the genotype-phenotype correlation is not always easy to assess. Diagnosis could require multiple analysis before the correct causative mutation is detected. Moreover, it seems that approximately 5% of overall diagnoses for genetic diseases involves multiple genomic loci, although they are often underestimated or underreported. In particular, the combination of multiple variants is rarely described in CMT pathology and often neglected during the diagnostic process. Here, we present the complex genetic analysis of a family including two CMT cases with various severities. Interestingly, next generation sequencing (NGS) associated with Cov'Cop analysis, allowing structural variants (SV) detection, highlighted variations in (microrchidia family CW-type zinc-finger 2) and (alanyl-tRNA-synthetase) genes for one patient and an additional mutation in (Mitofusin 2) in the more affected patient.
夏科-马里-图斯（CMT）病是一组影响周围神经系统的遗传性疾病，患病率为1/2500。到目前为止，已鉴定出80多个基因的突变可导致脱髓鞘型（CMT1）或轴索性（CMT2）。因此，基因型与表型的相关性并不总是容易评估。在检测到正确的致病突变之前，诊断可能需要进行多次分析。此外，似乎大约5%的遗传病总体诊断涉及多个基因组位点，尽管它们常常被低估或报告不足。特别是，多个变异的组合在CMT病理学中很少被描述，并且在诊断过程中常常被忽视。在这里，我们展示了一个家族的复杂基因分析，该家族中有两例严重程度不同的CMT病例。有趣的是，与Cov'Cop分析相关的下一代测序（NGS）能够检测结构变异（SV），结果显示一名患者的（微睾症家族CW型锌指蛋白2）和（丙氨酰-tRNA合成酶）基因存在变异，而病情更严重的患者在（线粒体融合蛋白2）中还存在另一个突变。
