二例COLQ基因突变所致的先天性肌无力综合征临床分析

Acetylcholinesterase-associated collagen-like tail subunit gene-related congenital myasthenic syndrome: a clinical analysis of two cases

目的分析乙酰胆碱酯酶相关的胶原尾部基因(COLQ)突变所致的先天性肌无力综合征(CMS)的临床、电生理、病理特点及基因突变情况,为提高该疾病的临床诊治水平提供参考依据。方法收集解放军总医院神经内科2017年10月、2018年2月收治的2例CMS患者临床资料,包括病史、实验室检查结果、电生理及肌肉病理检查结果;同时对患者行CMS相关基因检测。结果(1)患者1为10岁男性,自幼运动能力差,病情缓慢进展,伴步态异常。例2为30岁女性,22岁发病,临床表现为四肢无力及呼吸困难。(2)2例患者实验室检查示肌酶水平正常,新斯的明试验阴性,重症肌无力相关血清学指标阴性。电生理检查提示轻度肌源性损害,重频刺激示低频递减,肌肉活检可见散在肌纤维萎缩。2例患者均存在COLQ基因突变,患者1为复合杂合突变:c1274T>C及c.869G>A;患者2为纯合突变:c.1228C>T;2例患者均为错义突变。结论COLQ基因突变导致的CMS患者临床高度异质性,血清学指标阴性,电生理重频刺激低频递减,肌肉病理可见散在肌纤维萎缩,基因检测可明确诊断。

Objective To analyze the clinical, electrophysiological, pathological and genetic features of patients with acetylcholinesterase-associated collagen-like tail subunit gene (COLQ)-related congenital myasthenic syndrome(CMS), and provide references for improving the clinical diagnosis and treatments of this disease. Methods Two patients with CMS, admitted to our hospital in October 2017 and February 2018, were chosen in our study. The clinical data, including clinical history, laboratory examination, and electrophysiological and pathological characteristics, were collected. Next-generation gene sequencing and pedigree validation were performed on the patients to detect the CMS-related genes. Results (1) Patient one was a 10 year-old boy complaining of poor exercise capacity from birth, and he presented with abnormal gait, which developed slowly;patient two was a 30 year-old female whose manifestations were myasthenia of limbs and dyspnea when she was 22.(2) The laboratory examinations showed that muscle enzymes, neostigmine test, and antibodies against myasthenia gravis were normal;electrophysiological examination indicated slight myogenic damage, with decreased response of the low-frequency repetitive nerve stimulation;muscle biopsy showed scattered muscle fiber atrophy. Gene analysis revealed missense mutations in COLQ of two patients;patient one was a compound heterozygous mutations (c.1274T>Cand c.869G>A), and patient two was a homozygous mutation (c.1228C>T);both were missense mutations. Conclusions COLQ-related CMS patients have clinical heterogeneity, with negative blood tests, decrement of low-frequency repetitive nerve stimulation, and scattered muscle fiber atrophy of muscle biopsy. Next-generation gene sequencing can make a definite diagnosis.