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目的 对一祖孙四代的QT延长综合征 (LQTS)家系进行临床研究及分子遗传学分析 ,并揭示该家系成员基因型与基因表型之间的关系。方法 搜集整理先证者及该家系成员的临床资料 ,采用PCR SSCP进行基因突变位点的初步检测 ,并应用直接测序的方法进行验证。结果 该家系2 6例中达到临床诊断标准者 6例 ,可疑诊断 1例。其共同的心电图特征为 :QTc≥ 0 46s,T波宽大双峰 ,U波明显。基因检测结果表明 ,7例成员HERG基因的 10号外显子均出现一个新的单碱基的转换突变 (CGA2 5 87TGA) ,该无义突变导致快速激活延迟整流性钾通道 (IKr) ,缺失了 2 96个氨基酸。结论 该研究发现了LQTS一个新的致病基因突变位点 ,并验证了LQTS 2型患者的心电图特点。推测该家系中致病基因携带者心电图U波的出现可能同IKr蛋白质C末端的缺失有关。
Objective To study the clinical and molecular genetics of the QTLs of QT prolongation syndrome (LQTS) in four generations of ancestor and grandchildren and to reveal the relationship between genotypes and gene phenotypes in this pedigree. Methods The clinical data of probands and members of the pedigree were collected and analyzed. PCR SSCP was used to detect the gene mutation sites and verified by direct sequencing. Results The family of 26 cases reached clinical diagnostic criteria in 6 cases, suspicious diagnosis in 1 case. The common ECG features: QTc ≥ 0 46s, T wave width bimodal, U wave significantly. The result of gene test showed that there was a new single base transition mutation (CGA2 5 87TGA) in the HERG gene of all 7 members. This nonsense mutation resulted in rapid activation of delayed rectifier potassium channel (IKr) 2 96 amino acids. Conclusions This study identified a new site of disease-causing mutations in LQTS and validated the electrocardiographic features of LQTS type 2 patients. It is speculated that the occurrence of U wave of electrocardiogram in the pedigree of pathogenic gene may be related to the deletion of C terminal of IKr protein.