腓骨肌萎缩症合并小脑性共济失调的临床及遗传学特点

doi:10.3969/j.issn.1674-8115.2023.03.011

摘要/Abstract

摘要：

腓骨肌萎缩症（Charcot-Marie-Tooth disease，CMT）是一组以周围神经病变为主的遗传性运动感觉神经病。主要临床症状包括进行性对称性肢体远端无力、萎缩、感觉障碍和腱反射减退或消失。根据神经电生理表现和病理特点，CMT可分为以脱髓鞘为主的CMT1型和轴索病变为主的CMT2型。除了周围神经系统病变外，CMT部分表型可同时累及中枢神经系统或其他脏器；其中小脑系统受累的CMT患者同时合并小脑性共济失调，可见于神经丝蛋白轻链（neurofilament light chain，NEFL）基因突变所致的CMT1F型和CMT2E型，MORC家族CW型锌指结构蛋白2（MORC family CW-type zinc finger 2，MORC2）基因突变所致的CMT2Z型，溶质载体家族25成员46（solute carrier family 25 member 46，SLC25A46）基因突变所致的伴视神经萎缩的CMT6B型，以及多核苷酸激酶3′-磷酸酶（polynucleotide kinase 3′-phosphatase，PNKP）基因突变所致的CMT2B2型等。近年来，CMT重叠表型成为研究的热点，其中CMT合并小脑性共济失调具有高度临床异质性和遗传异质性，临床上易发生误诊。该文就合并小脑性共济失调的CMT表型的临床及遗传学特点进行综述，旨在为该类患者的早期诊断和治疗提供参考。

关键词: 腓骨肌萎缩症, 小脑性共济失调, 基因突变, 神经丝蛋白轻链, MORC家族CW型锌指结构蛋白2

Abstract:

Charcot-Marie-Tooth disease (CMT) is a group of hereditary motor and sensory neuropathy predominantly with peripheral neuropathy. It is characterized by progressive symmetric distal-predominant weakness, amyotrophy, sensory loss and reduced or absent deep tendon reflexes. CMT is usually divided into CMT1 type with demyelination and CMT2 type with axonal lesions according to electrophysiological and pathological characteristics. In addition to peripheral nervous system lesions, some CMT subtypes may also involve the central nervous system or other organs. The CMT patients with cerebellar system involvement also have cerebellar ataxia which can be seen as CMT1F type and CMT2E type caused by mutations in neurofilament light chain(NEFL) gene, CMT2Z with mutations in MORC family CW-type zinc finger 2 (MORC2) gene, CMT-6B with mutations in solute carrier family 25 member 46 (SLC25A46) gene, CMT2B2 with mutations in polynucleotide kinase 3′-phosphatase (PNKP) gene and so on. In recent years, CMT overlapping phenotypes have become a hot topic of research, among which CMT with cerebellar ataxia is a clinically and genetically heterogeneous group of disorders, and is prone to misdiagnosis clinically. This article reviews the clinical and genetic characteristics of CMT with cerebellar ataxia, aiming to provide reference for the earlier recognition and therapeutic strategies.

Key words: Charcot-Marie-Tooth disease (CMT), cerebellar ataxia, gene mutation, neurofilament light chain(NEFL), MORC family CW-type zinc finger 2 (MORC2)

中图分类号:

R746.4

朱啸巍, 钟平, 曹立, 栾兴华. 腓骨肌萎缩症合并小脑性共济失调的临床及遗传学特点[J]. 上海交通大学学报（医学版）, 2023, 43(3): 350-357.

ZHU Xiaowei, ZHONG Ping, CAO Li, LUAN Xinghua. Clinical and genetic characteristics of Charcot-Marie-Tooth disease with cerebellar ataxia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 350-357.

图/表 4

图1 NEFL的结构示意图及突变分布Note： CMT1F mutations are shown in blue; CMT2E mutations are shown in green and both in orange.

Fig 1 Structure diagram and mutation distribution of NEFL

图2 MORC2的结构示意图及突变分布Note： CC—coiled coil; S5—transducer S5-like domain; CW—zinc finger domain; CD—coil domain.

Fig 2 Structure diagram and mutation distribution of MORC2

图3 SLC25A46的结构示意图及突变分布Note： MC—mitochondrial carrier domain.

Fig 3 Structure diagram and mutation distribution of SLC25A46

图4 PNKP的结构示意图及突变分布Note： FHA—forkhead associated domain.

Fig 4 Structure diagram and mutation distribution of PNKP

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