家族性高钾型周期性麻痹的SCN4A基因突变  

Screening SCN4A gene for mutations in a Chinese family with hyperkalemic periodic paralysis

作　　者：郭秀海[1] 吴卫平[1] 丁素菊[2] 张雁华[3] 朱克[1] 

机构地区：[1]解放军总医院神经内科 [2]第二军医大学长海医院神经内科 [3]解放军总医院麻醉科,北京100853

出　　处：《中华神经科杂志》2005年第4期228-231,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目(30370495)

摘　　要：目的　筛查1个高钾型周期性麻痹(hyperkalemicperiodicparalysis, hyperKPP)家系的SCN4A基因,明确该病与SCN4A基因的关系。方法　总结1个hyperKPP家系中7例患者的临床特点,应用变性液相色谱(denaturinghighperformanceliquidchromatography,DHPLC)技术筛查SCN4A基因全部24个外显子,对发现异常洗脱峰者进行连锁分析并测序。结果　该家系具有典型hyperKPP临床特征,但无肌强直。先证者经DHPLC筛查发现在外显子13、23及24存在杂合二倍体。测序及连锁分析证实位于外显子13的碱基替换引起氨基酸序列改变(Thr704Met);外显子23的碱基替换虽引起氨基酸序列改变(Asp1376Asn)与疾病连锁,但进一步研究显示其为一良性多态;外显子24的碱基替换为同义突变。结论　该家族性hyperKPP与SCN4A基因相关,并由最常见的突变Thr704Met引起。Objective To study the clinical features of hyperkalemic periodic paralysis (hyperKPP) and the relationship with SCN4A gene in a Chinese family Methods The clinical features of 7 patients in a Chinese family with hyperKPP were summarized All 24 exons of SCN4A gene were screened with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal elution peak Results This family showed typical clinical features of hyperKPP but without myotonia Three mutations were found in exon 13, 23 and 24 respectively Linkage analysis and direct sequencing showed the mutation in exon 24 was a synonymous mutation The mutation in exon 23 was a missense mutation, but proved to be a benign polimophism; the mutation in exon 13 was proved leading to the best known amino acid exchange Thr704Met Conclusion SCN4A gene should be related to hyperKPP, and Thr704Met be responsible for hyperKPP in this Chinese family

关 键 词：周期性麻痹 高钾型 家族性 基因突变 SCN4A基因 performance 氨基酸序列 连锁分析 外显子 DHPLC 临床特点 液相色谱 high 临床特征 筛查 家系 先证者 肌强直 碱基 二倍体 步研究 测序 

分 类 号：R746.3[医药卫生—神经病学与精神病学] R734.2[医药卫生—临床医学]