结节性硬化症的两个TSC2基因新发框移突变

发布时间：2018-12-06 20:11

【摘要】：该研究采用高通量测序对两个结节性硬化症(TSC)家系先证者外周血DNA行TSC相关基因(TSC1、TSC2)及其拼接序列检测,确定基因突变位点,针对突变位点设计扩增引物,采用聚合酶链反应和Sanger测序法对先证者及其父母外周血DNA行一代测序验证。两家系先证者分别存在TSC2基因c.3981-3982ins A(p.Asp1327Aspfs X87)、c.4013-4014 delCA(p.Ser1338Cysfs)杂合突变。家系1先证者父母该位点均未见异常;家系2先证者母亲检出TSC2基因c.4013-4014 delCA杂合突变,先证者父亲、先证者外祖父母该位点未见异常。c.3981-3982 insA突变会导致氨基酸序列在第1413位提前终止编码,c.4013-4014 delCA突变导致氨基酸序列在第1412位提前终止编码,二者分别为家系1、家系2的致病突变,且均为新发框移突变,但与疾病的关系仍需要突变蛋白功能细胞模型和动物模型的进一步验证。
[Abstract]:In this study, high throughput sequencing was used to detect the TSC related gene (TSC1,TSC2) and its splicing sequence in peripheral blood DNA of two (TSC) probands with nodular sclerosis. The mutation sites were identified and amplified primers were designed for the mutation sites. Polymerase chain reaction (PCR) and Sanger sequencing were used to verify the peripheral blood DNA of the proband and their parents. The TSC2 gene c.3981-3982ins A (p.Asp1327Aspfs X87) and c. 4013-4014 delCA (p.Ser1338Cysfs) were heterozygous in the two families. No abnormal locus was found in the parents of the proband in pedigree 1. The TSC2 gene c. 4013-4014 delCA heterozygosity was detected by the mother of the second proband. The father of the proband and the maternal grandparent of the proband had no abnormality at this locus. The mutation of c. 3981-3982 insA led to the early termination of the amino acid sequence at the 1413 position. The mutation of c. 4013-4014 delCA resulted in the early termination of the amino acid sequence at the 1412 position, both of which were pathogenicity mutations of family 1 and family 2, and were both new frame shift mutations. But the relationship with disease still needs further verification of mutant protein functional cell model and animal model.
【作者单位】：南方医科大学附属深圳妇幼保健院产前诊断中心;深圳市出生缺陷预防控制重点实验室;
【基金】：2015年度深圳市卫生计生系统科研项目/重点学科建设能力提升项目(201506062) 深圳市科技计划基础研究项目(JCYJ20150402090413001)
【分类号】：R725.9

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