CAJ | 학술논문

目的探讨CHRNE基因突变导致的先天性肌无力综合征的临床表现和电生理改变特点.方法对3例先天性肌无力综合征患者的临床、实验室检查、电生理特点进行了描述.提取外周血单核细胞DNA,对CHRNE基因12个外显子进行了测序分析.结果 3例患者均为女性,发病年龄20 ～ 30岁,主要临床表现包括四肢无力、眼肌麻痹以及言语不清;实验室检查重症肌无力相关的血清学检查全部阴性;电生理检查显示2例患者存在低频重频递减现象及肌源性损害;所有患者对胆碱酯酶抑制剂均有显著疗效.3例患者的CHRNE基因检测发现多个位点错义突变,其中c.488 C＞T为国外已报道突变,而c.296 G＞A、c.738 C＞A目前国内外均尚未见报道,我们随即对120名健康人DNA进行了后2种突变的筛查,发现该突变仅存在于患者中,健康人群并未检测到这2种突变的发生.结论我们报道的这3例由CHRNE突变导致的先天性肌无力综合征均为成年起病,病程相对良性,临床症状表现类似重症肌无力,电生理检查可见低频重频递减现象,长病程患者可见肌源性损害,但血清学检查阴性及对胆碱酯酶抑制剂的良好反应为其特点.目前国内尚未见该病基因确诊病例报道,关于该病在我国的发病率、临床及分子生物学特点值得进一步研究.
목적 탐토CHRNE기인돌변도치적선천성기무력종합정적림상표현화전생리개변특점.방법 대3례선천성기무력종합정환자적림상、실험실검사、전생리특점진행료묘술.제취외주혈단핵세포DNA,대CHRNE기인12개외현자진행료측서분석.결과 3례환자균위녀성,발병년령20 ～ 30세,주요림상표현포괄사지무력、안기마비이급언어불청;실험실검사중증기무력상관적혈청학검사전부음성;전생리검사현시2례환자존재저빈중빈체감현상급기원성손해;소유환자대담감지매억제제균유현저료효.3례환자적CHRNE기인검측발현다개위점착의돌변,기중c.488 C＞T위국외이보도돌변,이c.296 G＞A、c.738 C＞A목전국내외균상미견보도,아문수즉대120명건강인DNA진행료후2충돌변적사사,발현해돌변부존재우환자중,건강인군병미검측도저2충돌변적발생.결론 아문보도적저3례유CHRNE돌변도치적선천성기무력종합정균위성년기병,병정상대량성,림상증상표현유사중증기무력,전생리검사가견저빈중빈체감현상,장병정환자가견기원성손해,단혈청학검사음성급대담감지매억제제적량호반응위기특점.목전국내상미견해병기인학진병례보도,관우해병재아국적발병솔、림상급분자생물학특점치득진일보연구.
Objective To explore the clinical and electrophysiological features in patients with congenital myasthenic syndrome (CMS) due to CHRNE gene mutation.Methods We reported the clinical,laboratory and electrophysiological characteristics in 3 patients with CMS.We also sequenced twelve exons of CHRNE gene by extracting the DNA of peripheral blood mononuclear cell.Results The three patients are all females.The age of onset rangs from twenty to thirty.The main clinical characteristics of the patients included muscular weakness,ophthalmoplegia and slurred speech.All the antibodies against acetylcholine receptor and muscle-specific receptor tyrosine kinase were negative.In electrophysiological examination 2 patients showed decrement in low frequency repetitive stimulation and myogenic damage.Cholinesterase inhibitors were efficient in all 3 patients.Under the sequence of CHRNE genes,many missense mutations were found,in which c.488 C ＞ T has been reported before,but c.296 G ＞ A and c.738 C ＞A have not been described yet.Then we screened the 2 new mutations in 120 healthy persons,and finally found that these two mutations were only found in the patients.Conclusions The 3 patients of CMS due to CHRNE gene mutations in our research have the following features:The onset was in adult,and all had a relatively benign course; The clinical manifestations were similar to myasthenia gravis,the electrophysiological examination showed decrement in low frequency repetitive stimulation,and myogenic damage could be found in long-course patients.All the antibodies against acetylcholine receptor and musclespecific receptor tyrosine kinase were negative,and cholinesterase inhibitors were efficient in all three patients.CMS patient diagnosed by genetic methods has never been reported in China up to now,and the incidence,clinical and molecular biological features of CMS in China need to be further investigated.