摘要
目的检测中国人家族性扩张型心肌病核纤层蛋白A(Lamin A)基因(LMNA)突变情况并初步探索突变基因功能。方法(1)用基因测序的方法扫描1个中国人扩张型心肌病家系(50名成员)LMNA基因的12个外显子,对照为60例正常志愿者。(2)构建野生及突变LMNA基因的真核表达载体并分别转染HEK293细胞后,用0.8mmol/L过氧化氢刺激24h,观察各组细胞凋亡率的差异。结果(1)该家系先证者LMNA基因第1号外显子第244位碱基位置发生G→A转换,其编码氨基酸由谷氨酸(E)变为赖氨酸(K)。(2)给予0.8mmol/L过氧化氢刺激24h后,转染突变LMNA基因表达载体的细胞组凋亡率(29.13±1.24)%显著高于其他细胞组(P<0.01)。结论携带LMNA基因E82K错义突变的患者临床表型呈现症状重、发病早、预后差的临床特点,且部分患者合并Ⅱ°～Ⅲ°房室传导阻滞,该突变所促进的细胞凋亡可能是导致扩张型心肌病的原因之一。
Objective To examine the function of the novel mutation E82K in LMNA gene identified in a Chinese family infected by dilated cardiomyopathy. Methods （1） One Chinese family infected by dilated cardiomyopathy was chosen for the study. Exons 1-12 of the LMNA gene were screened with both PCR method and the cycle sequencing of the PCR products. （2） cDNA of the E82K mutation or wild type of LMNA gene was transfected into HEK293 cells and the apoptosis of the cells was detected after treatment with 0. 8 mmol/L H2O2. Results （ 1 ） A new mutation E82K in LMNA gene was identified in this dilated cardiomyopathy family. （2） Apoptosis was more in the HEK293 cells transfected with E82K mutation than those with empty vector or wild type LMNA gene. Conclusions The missense mutation E82K in LMNA gene changed the polar of the amino acid. It showed a malignant phenotype of severe clinical symptoms, early onset, poor survival prognosis and might be associated with atrioventricular conduction block （ Ⅱ°-Ⅲ°）, suggesting that the E82K mutation in LMNA gene may be a candidate for nosogenesis of dilated cardiomyopathy.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2005年第10期875-879,共5页
Chinese Journal of Cardiology
基金
北京市重大自然科学基金资助项目(7040001)
关键词
心肌病
充血性
突变
LMNA
Cardiomyopathy, congestive
Mutation
LMNA
