论文部分内容阅读
目的:对29个结节性硬化症(tuberous sclerosis complex，TSC)家系进行TSC1、TSC2基因的变异筛查，并对其中14个家系的高危胎儿进行产前诊断，探讨二代测序(next generation sequencing，NGS)联合多重连接探针扩增(multiple ligation-dependent probe amplification，MLPA)对TSC相关变异的筛查效果。方法:采用NGS-Sanger测序和MLPA技术对29个家系的先证者进行TSC1/TSC2基因的变异检测；抽取胎儿羊水或绒毛样本，通过亲子鉴定试验排除母体污染；针对先证者携带的致病变异对胎儿进行基因诊断。结果:在29个TSC家系中共检出27种疑似致病变异，其中TSC1变异5种(18.5%)，TSC2变异22种(81.5%)，12种未见文献报道。14个接受产前诊断的家系中，5个家系的胎儿为患者，其中2例胎儿携带TSC2基因新发变异，超声提示心脏多发横纹肌瘤，其余9个家系的胎儿判断为正常。结论:本研究拓展了TSC1、TSC2基因的变异谱。高通量测序结合MLPA可以高效、准确地为TSC患者提供基因诊断。“,”Objective:To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis.Methods:NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands.Results:Twenty seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected.Conclusion:Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.