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目的应用基因筛查技术对1个遗传性长QT综合征(LQTS)患病家系进行12个已知致病基因的突变分析,明确致病突变。方法在符合伦理要求和获得知情同意的情况下,经过详细的病史采集及临床检查后,采集该家系中7名患者和1名表型正常个体外周血并提取基因组DNA。利用Complete Genomics测序平台对先证者进行全基因组测序,分析已知致病基因:KCNQ1、KCNH2、SCN5A、ANK2、KCNE1、KCNJ2、CACNA1C、CAV3、SCN4B、AKAP9、SNTA1、KCNJ5。对于定位于先证者中的突变,用聚合酶链式反应和直接测序法在家系中其他成员中进行测序,最终确定致病基因突变位点。结果在该家系患者的KCNH2基因上发现1个移码突变c.2400delC(p.Gly800fs*10),在家系内正常成员和正常人群中均未发现该突变。结论在1个中国LQTS家系中发现了一个LQTS相关的KCNH2基因新突变(del D1790)。
Objective To analyze the mutation of 12 known virulence genes in one hereditary long QT syndrome (LQTS) affected by gene screening and to confirm the pathogenic mutation. Methods After ethical requirements and informed consent were obtained, seven patients in the pedigree and one normal phenotype in peripheral blood were collected and genomic DNA was extracted after a detailed history collection and clinical examination. Complete Genomics sequencing platform was used to carry out genome-wide sequencing of probands to analyze the known causative genes: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, KCNJ5. For mutations located in probands, polymerase chain reaction and direct sequencing are used to sequence among other members of the pedigree to determine the site of disease-causing mutations. Results A mutation of c.2400delC (p.Gly800fs * 10) was found in the KCNH2 gene in this pedigree. No mutation was found in the normal and normal controls of the pedigree. Conclusions A novel LQTS-associated KCNH2 gene mutation (del D1790) was found in one Chinese LQTS pedigree.