X连锁遗传的Emery-Dreifuss肌营养不良一家系的临床、病理及基因突变特点

目的报道1例X连锁遗传的Emery-Dreifuss肌营养不良(X-EDMD)患者家系的临床、病理及基因突变特点。方法总结作者单位收治的1例X-EDMD患者的临床及骨骼肌病理特点,并进行EMD及LMNA基因突变检测,同时对患者家系谱进行分析。结果该家系中有4例患者,主要表现为缓慢型心律失常,2例已猝死,先证者同时有轻度肘关节挛缩及肌萎缩。先证者心电图检查示房性心动过速合并Ⅲ度房室阻滞,交界区逸搏心律;超声心动图检查示全心扩大,二尖瓣及三尖瓣A峰消失,射血分数60%。肌电图检查示右肱二头肌、左第一骨间肌、左腓肠肌、左股四头肌运动单位电压均增高,神经传导未见异常。左肱二头肌活检示肌营养不良样改变,免疫组化染色显示肌核无伊默菌素蛋白表达。基因分析显示先证者存在EMD基因插入突变c.650_654dupTGGGC,为已报道的致病性突变,LMNA基因均未发现致病性突变。结论 EMD基因c.650_654dup TGGGC插入突变导致的X-EDMD患者心脏损害突出,以心房的电活动-机械活动及结构的严重受累为特征,而肌萎缩及关节挛缩症状相对轻微。

The clinical,myopathological and genetic features of a family with X-linked Emery-Dreifuss muscular dystrophy

Objective To report the clinical,pathological and genetic features of a Chinese family with X-linked Emery-Dreifuss muscular dystrophy (X-EDMD).Methods The clinical and muscular pathological features of a family with X-EDMD were summarized.The sequence of EMD and LMNA gene was analyzed after genomic DNA was extracted from the white blood cells of the proband.Results The four affected members in the family mainly manifested as bradycardia,two of which underwent sudden cardiac death.The proband also had mild contracture of elbow and muscular atrophy.Electrocardiogram showed atrial tachycardia accompanied by third-degree atrioventricular block with a junctional escape rhythm.Echocardiography revealed enlargement of the whole heart and lack of "A" wave in the Doppler mitral/tricuspid flow pattern,with an ejection fraction of 60％.Electromyography disclosed high potential of motor unit in right biceps,left first dorsal interosseous,left gastrocnemius muscles and left quadriceps,with normal nerve conduction velocities.The biopsy of left biceps disclosed muscular dystrophy.Immunohistochemistry showed deficient expression of emerin in all nuclei of muscle fibers.Genetic analysis revealed a pathogenic insertion mutation,c.650 _ 654dupTGGGC,in EMD gene in the proband,and no mutation in LMNA gene.Conclusions The insertion mutation of c.650 _ 654dupTGGGC in EMD gene resulted in a family with X-EDMD.The affected members suffered from severe cardiac involvement which was characterized by serious damage of atrial electrical activity,mechanical activity and structure,as well as mild muscular atrophy and joint contracture.