CHRNE基因突变导致的先天性肌无力综合征的临床和电生理分析  

Clinical and electrophysiological analysis of congenital myasthenic syndrome due to CHRNE gene mutation

作　　者：苏净[1] 李传芬[1] 陶珍[1] 王敏[1] 李慎军[1] 刘付红[1] 李靖[1] 曹秉振[1] 

机构地区：[1]济南军区总医院神经内科,250031

出　　处：《中华神经科杂志》2014年第12期847-851,共5页Chinese Journal of Neurology

摘　　要：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.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.

关 键 词：肌无力综合征 先天性 受体 烟碱 突变 电生理学 

分 类 号：R746.1[医药卫生—神经病学与精神病学] R445.2[医药卫生—临床医学]