基因筛查在长QT综合征诊断和治疗中的应用

目的 明确基因筛查对先天性和获得性长QT综合征(LQTS)诊断和治疗意义。方法 应用PCR方法扩增位于LQT1、LQT2和LQT3基因内和临近的9个短串联重复序列(short tandem repeats，STR)位点后．行染色体单倍型连锁分析；HERG基因外显子的PCR产物直接测序。结果 3位患者携带缺失19个碱基的HERG突变基因，该致病基因来自于父系家族。结论 基因筛查进行早期和准确的诊断。从而对LQTS患者实施个体化的治疗方案。

Clinical and genetic analysis of long QT syndrome in a Chinese family

Objective LQTS are genetically and clinically heterogeneous. The affected gene in any patient can lead to a various clinical presentation and outcomes depending on its specific mutations. The object of this study is to assess the importance of the molecular study for the LQTS patients. Methods Subjects underwent detailed clinical examination including resting body surface ECG. The QT intervals were manually measured (usually in lead II or V5) and corrected by heart rate (QTc) using Bazett's formula. Genomic DNA was extracted from blood sample by standard procedure. STR markers (D7S1824, D7S2439, D7S483, D3S1298, D3S1767,D3S3521) in or spanning theKCNQ1,HERG and SCN5A were amplified, Mutation identified by cloning and sequencing. Results Genotype showed a linkage to chromosome 7q35-36, where the potassium channel gene KCNH2 is encoded. 3 gene carriers were identified. 1 patient and 9 suspicious patients were excluded. A 19-base pair (CCGTACTCTGAGTAGCGAT) deletion at nucleotide position 1619-1637 in pore helix was identified. Conclusion Molecular study can provide useful tool for the presymptomatic and accurate diagnosis for LQTS. It allows sophisticated clinical management tailored toward the specific, genetically controlled, characteristics of each patient.