正常血钾型周期性麻痹SCN4A基因新突变的检测  

The detection of a novel mutation by screening SCN4A gene in normokalemic periodic paralysis

作　　者：郭秀海[1] 吴卫平[1] 张雁华[2] 朱克[1] 

机构地区：[1]解放军总医院神经内科,北京100853 [2]解放军总医院麻醉科,北京100853

出　　处：《中华神经科杂志》2004年第3期199-202,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目 (3 0 3 70 495 ) ;军队十五医药卫生重点课题基金资助项目 (0 1Z0 41)

摘　　要：目的　报道正常血钾型周期性麻痹 (normoPP)一家系的临床特点 ,并筛查SCN4A基因以期发现有义突变。方法　提取知情同意的患者及部分家属外周血基因组DNA ,应用变性高效液相色谱分析 (DHPLC)技术筛查患者SCN4A基因全部 2 4个外显子 ,对发现异常者进行测序分析。结果先证者常规实验室检查未见异常 ,发作期肌酸激酶 (CK) 112 6U/L(正常值 <2 0 0U/L) ,肌电图正常。发作间期行肌肉活检未见显著异常。基因研究发现先证者及其父亲 (患者 )SCN4A基因发生同一新突变G2 10 1A ,并引起氨基酸序列改变Arg6 75Gln。该突变不同于目前发现的明确导致高钾型周期性麻痹(hyperPP)的突变 ,也不同于已知的SCN4A基因所有突变。结论　normoPP患者存在一新突变Arg6 75Gln ,该突变可能与疾病相关。Objective To detect a novel mutation in SCN4A gene related to normokalemic periodic paralysis (normoPP) in one Chinese family.Methods Genomic DNA of two patients and their relatives in this family was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction (PCR). All 24 exons of SCN4A gene were screened with denaturing high performance liquid chromatography (DHPLC) technology,and then sequence analysis of those DHPLC chromatograms showing heteroduplex were compared with the unaffected controls.Results Routine laboratory tests were carried on within normal ranges with the exception of an elevated creatine kinase (1126 U/L,normal <200 U/L) during an attack of weakness to the proband. Electromyograms and electrocardiograms were normal. Muscle biopsy showed no changes by light microscopy. A novel mutation G2101A predicting the amino acid exchange Arg675Gln in the segment 4 of domain Ⅱ of SCN4A was detected in both patients.Conclusions This novel mutation Arg675Gln should exist in Chinese patients,and might lead to normoPP.

关 键 词：正常血钾型周期性麻痹 SCN4A基因 突变 检测 变性高效液相色谱 

分 类 号：R746[医药卫生—神经病学与精神病学]