13例早发型腓骨肌萎缩症的基因分型研究

目的 探讨早发型腓骨肌萎缩症（CMT）的临床特征及遗传变异分析。方法 以临床诊断为早发型CMT的患儿为研究对象,收集相关临床资料,进行肌电图及CMT相关基因检测并分析。结果 早发型CMT病例共13例,男9例（69%）,女4例（31%）,平均就诊年龄4.0±2.1岁,其中12例（92%）患儿起病年龄 < 2岁。9例（69%）诊断为CMT1型（其中Dejerine-Sottas综合征6人）,1例（8%）为中间型,3例（23%）为CMT2型。13例患儿的基因检测结果显示6例（46%）患儿存在外周髓鞘蛋白22（PMP22）基因重复突变、3例（23%）髓鞘蛋白零（MPZ）基因插入突变及点突变、3例（23%）线粒体融合蛋白2（MFN2）基因点突变、1例（8%）人轻肽神经丝蛋白（NEFL）基因点突变,其中11例（85%）为已知致病突变,2例（15%）为新变异。MPZ基因新变异c.394C > G（p.P132A）评级为"可能致病的"及MFN2基因新变异c.326A > G（p.K109R）评级为"致病的"。结论 早发型CMT以PMP22基因重复突变及MPZ基因突变为主,临床分型以CMT1型为主,其中Dejerine-Sottas综合征占有相当比例。

A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease

Objective To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). Methods Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. Results A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C > G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A > G (p.K109R) of the MFN2 gene was rated as "pathogenic". Conclusions Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.