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Abstract：
Peripheral neuropathies of genetic etiology are a very diverse group of disorders manifesting either as non-syndromic inherited neuropathies without significant manifestations outside the peripheral nervous system, or as part of a systemic or syndromic genetic disorder. The former and most frequent group is collectively known as Charcot-Marie-Tooth disease (CMT), with prevalence as high as 1:2,500 world-wide, and has proven to be genetically highly heterogeneous. More than 100 different genes have been identified so far to cause various CMT forms, following all possible inheritance patterns. CMT causative genes belong to several common functional pathways that are essential for the integrity of the peripheral nerve. Their discovery has provided insights into the normal biology of axons and myelinating cells, and has highlighted the molecular mechanisms including both loss of function and gain of function effects, leading to peripheral nerve degeneration. Demyelinating neuropathies result from dysfunction of genes primarily affecting myelinating Schwann cells, while axonal neuropathies are caused by genes affecting mostly neurons and their long axons. Furthermore, mutation in genes expressed outside the nervous system, as in the case of inherited amyloid neuropathies, may cause peripheral neuropathy resulting from accumulation of β-structured amyloid fibrils in peripheral nerves in addition to various organs. Increasing insights into the molecular-genetic mechanisms have revealed potential therapeutic targets. These will enable the development of novel therapeutics for genetic neuropathies that remain, in their majority, without effective treatment.
摘要：
遗传病因的周围神经病变是一组非常多样化的疾病，表现为非综合征性遗传性神经病，在周围神经系统之外没有明显的表现。或作为系统性或综合征性遗传疾病的一部分。前者和最常见的群体统称为Charcot-Marie-Tooth病（CMT），全球患病率高达1:2500，并被证明是基因高度异质的。到目前为止，已经鉴定出100多个不同的基因来引起各种CMT形式，遵循所有可能的继承模式。CMT致病基因属于几种常见的功能途径，对周围神经的完整性至关重要。他们的发现为轴突和髓鞘细胞的正常生物学提供了见解，并强调了分子机制，包括功能丧失和功能获得效应，导致周围神经变性.脱髓鞘性神经病是由主要影响髓鞘化雪旺细胞的基因的功能障碍引起的。而轴突神经病是由影响大部分神经元及其长轴突的基因引起的。此外，在神经系统外表达的基因突变，就像遗传性淀粉样神经病一样，除各种器官外，还可能由于β结构淀粉样原纤维在周围神经中的积累而引起周围神经病变。越来越多的对分子遗传机制的了解揭示了潜在的治疗靶点。这些将有助于开发新的遗传性神经病的治疗方法，在大多数情况下，没有有效的治疗。
