检索历史 清除

目的 探讨骨骼肌钠离子通道病的临床特征、骨骼肌病理改变和电压门控钠通道α亚单位(SCN4A)基因突变特点.方法 收集北京大学第一医院神经内科2007-2012年经基因诊断的14个骨骼肌钠离子通道病家系的17例患者(男性14例,女性3例)的临床资料,中位发病年龄为3.0(1.0,11.5)岁,其中正常血钾型周期性瘫痪10例,低钾型周期性瘫痪3例,周期性瘫痪型副肌强直2例,高钾型周期性瘫痪1例,先天性副肌强直1例;伴随持续性肌无力患者13例.对所有患者进行SCN4A基因突变检查.对15例患者行肌肉活体组织检查.结果 伴有和不伴有持续性肌无力的两组患者发病年龄为2.0(1.0,4.5)岁和13.5(10.8,18.5)岁,两组相比差异有统计学意义(U=1.500,P =0.002).8例肌肉活体组织检查出现肌纤维空泡变和管聚集,均伴有持续性肌无力.无持续性肌无力的4例患者肌肉活体组织检查正常.在所有患者中发现9种SCN4A突变,其中p.L58X、p.M403L、p.L689F和p.M1323I为新突变.p.T704M出现在6个家系中.结论 我国SCN4A基因突变导致多种临床表型,持续性肌无力多出现在早发病患者中,其肌肉常出现空泡变或管聚集.p.T704M是本组患者最常见的突变类型.

Objective To report the features of clinical,myopathological and sodium channel α-subunit encoding gene (SCN4A) mutations from a group of Chinese patients with skeletal muscle sodium channelopathies.Methods Seventeen cases (14 males and 3 females) from 14 families with confirmed SCN4A mutations were enrolled in this study who were diagnosed in our department from 2007 to 2012.The median age of onset was 3.0 (1.0,11.5) years.Ten patients presented with normokalemic periodic paralysis,three with hypokalemic periodic paralysis,two with paralysis periodic paramyotonia congenita,one with hyperkalemic periodic paralysis,one with paramyotonia congenita.Thirteen of them had permanent weakness.Skeletal muscle biopsies were performed in 15 and SCN4A mutation screening was performed in all patients.Results The age of onset was 2.0(1.0,4.5) years and 13.5 (10.8,18.5) years respectively in patients with and without permanent weakness,indicating statistically difference between the two groups (U =1.500,P--0.002).Muscle biopsies revealed pathological changes including vacuoles or tubular aggregate in muscle fibers in 8 of 11 patients with permanent weakness,no specific change in four patients without permanent weakness.All patients were identified carrying SCN4A mutations,totally 9 different mutations,among which p.L58X,p.M403L,p.L689F and p.M1323I were novel mutations.It was noteworthy that p.T704M mutation appeared in 6 families.Conclusions SCN4A mutations can lead to heterogeneous phenotypes in Chinese patients with sodium channelopathies.Permanent weakness usually present in patients with early onset and with pathological muscle changes including vacuoles and tubular aggregates.The p.T704M mutation is the most common in the present series.