Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neurological disorders and can be caused by mutations in over 100 different genes. One of the causative genes is NEFL on chromosome 8 which encodes neurofilament light protein (NEFL), one of five proteins that co-assemble to form neurofilaments. At least 34 different CMT-causing mutations in NEFL have been reported which span the head, rod, and tail domains of the protein. The majority of these mutations are inherited dominantly, but some are inherited recessively. The resulting disease is classified variably in clinical reports based on electrodiagnostic studies as either axonal (type 2; CMT2E), demyelinating (type 1; CMT1F), or a form intermediate between the two (dominant intermediate; DI-CMTG). In this article, we first present a brief introduction to CMT and neurofilaments. We then collate and analyze the data from the clinical literature on the disease classification, age of onset and electrodiagnostic test results for the various mutations. We find that mutations in the head, rod, and tail domains can all cause disease with early onset and profound neurological impairment, with a trend toward greater severity for head domain mutations. We also find that the disease classification does not correlate with specific mutation or domain. In fact, different individuals with the same mutation can be classified as having axonal, demyelinating, or dominant intermediate forms of the disease. This suggests that the classification of the disease as CMT2E, CMT1F or DI-CMTG has more to do with variable disease presentation than to differences in the underlying disease mechanism, which is most likely primarily axonal in all cases.

中文翻译：

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神经丝蛋白L突变所致Charcot-Marie-Tooth病临床文献回顾与分析

Charcot-Marie-Tooth 病 (CMT) 是最常见的遗传性神经系统疾病之一，可由 100 多种不同基因的突变引起。致病基因之一是NEFL在编码神经丝轻蛋白 (NEFL) 的 8 号染色体上，NEFL 是共同组装形成神经丝的五种蛋白质之一。已经报道了 NEFL 中至少 34 种不同的 CMT 引起突变，这些突变跨越蛋白质的头部、杆状和尾部结构域。这些突变中的大多数是显性遗传的，但有些是隐性遗传的。在基于电诊断研究的临床报告中，由此产生的疾病被可变地分类为轴突（2 型；CMT2E）、脱髓鞘（1 型；CMT1F）或两者之间的中间形式（显性中间体；DI-CMTG）。在本文中，我们首先简要介绍 CMT 和神经丝。然后，我们整理和分析临床文献中有关各种突变的疾病分类、发病年龄和电诊断测试结果的数据。我们发现头域、杆域和尾域中的突变都可能导致早期发病和严重神经损伤的疾病，并且头域突变的严重程度有增加的趋势。我们还发现疾病分类与特定突变或域无关。事实上，具有相同突变的不同个体可被归类为具有轴突、脱髓鞘或显性中间形式的疾病。这表明将疾病分类为 CMT2E、CMT1F 或 DI-CMTG 与可变的疾病表现有更多关系，而不是与潜在疾病机制的差异有关，这很可能在所有情况下主要是轴突。头域突变有更严重的趋势。我们还发现疾病分类与特定突变或域无关。事实上，具有相同突变的不同个体可以被归类为具有轴突、脱髓鞘或显性中间形式的疾病。这表明将疾病分类为 CMT2E、CMT1F 或 DI-CMTG 与可变的疾病表现有更多关系，而不是与潜在疾病机制的差异有关，这很可能在所有情况下主要是轴突。头域突变有更严重的趋势。我们还发现疾病分类与特定突变或域无关。事实上，具有相同突变的不同个体可以被归类为具有轴突、脱髓鞘或显性中间形式的疾病。这表明将疾病分类为 CMT2E、CMT1F 或 DI-CMTG 与可变的疾病表现有更多关系，而不是与潜在疾病机制的差异有关，这很可能在所有情况下主要是轴突。