Echaniz-Laguna A
Département de Neurologie, Hôpitaux Universitaires, Hôpital de Hautepierre, 1, avenue Molière, 67098 Strasbourg, France; Centre de Référence des Maladies Neuromusculaires Grand-Est (CERNEST), Hôpital de Hautepierre, 1, avenue Molière, 67098 Strasbourg, France.
Rev Neurol (Paris). 2015 Jun-Jul;171(6-7):498-504. doi: 10.1016/j.neurol.2014.12.003. Epub 2015 Apr 18.
Molecular studies have created a paradigm shift in our perception of Charcot-Marie-Tooth disease (CMT). Indeed, CMT has evolved from the concept of a rather homogeneous hereditary disease exclusively involving peripheral nerves to the concept of a highly heterogeneous clinical and genetic syndrome mainly - but sometimes not exclusively - involving the peripheral nervous system. The phenotypic spectrum of CMT overlaps with other inherited neuropathies such as distal hereditary motor neuropathy (dHMN), hereditary sensory and autonomic neuropathy (HSAN), spinal muscular atrophy (SMA) subtypes, and the neuropathies of mitochondrial disorders. At a molecular level, mutations in one given gene may alternatively provoke CMT, HSAN, dHMN or SMA variants. Over the last years, there have been dramatic advances in deciphering the molecular basis for many CMT subtypes and more than 900 different mutations in more than 60 causative genes are now described. However, as 75% of CMT causative genes apparently remain unknown and as disease-specific therapies are not available, major advances are yet to come in the field of CMT.
分子研究使我们对夏科-马里-图斯病（CMT）的认识发生了范式转变。的确，CMT已经从一种仅累及周围神经的相当同质化的遗传性疾病的概念，演变为一种高度异质性的临床和遗传综合征的概念，主要（但并非总是唯一）累及周围神经系统。CMT的表型谱与其他遗传性神经病重叠，如远端遗传性运动神经病（dHMN）、遗传性感觉和自主神经病（HSAN）、脊髓性肌萎缩（SMA）亚型以及线粒体疾病的神经病。在分子水平上，一个特定基因的突变可能会引发CMT、HSAN、dHMN或SMA变体。在过去几年中，在破译许多CMT亚型的分子基础方面取得了巨大进展，现在已经描述了60多个致病基因中的900多种不同突变。然而，由于75%的CMT致病基因显然仍然未知，并且由于尚无针对该疾病的特异性疗法，CMT领域仍有待取得重大进展。
