解放军医学院学报2017，Vol.38Issue(1)：14-18,21,6.DOI:10.3969/j.issn.2095-5227.2017.01.004
新一代测序技术无创产前检测胎儿FGFR3基因突变
Accuracy and feasibility of non-invasive prenatal testing for FGFR3-related skeletal dysplasia by next-generation sequencing
任远 1高雅 1卢彦平 1赵佳 1李芮冰 1刘弘泰 1姜淑芳 1谢一帆 1周红辉1
作者信息
- 1. 解放军总医院 妇产科,北京 100853
- 折叠
摘要
Abstract
Objective To explore the test accuracy and feasibility of non-invasive prenatal testing for FGFR3- related skeletal dysplasia based on next-generation sequencing (NGS).Method Fragmented fetal genome DNA (gDNA) of achondroplasia (n=4) or thanatophoric dysplasia typeⅠ(n=2) were diluted by corresponding post-delivery maternal cell-free DNA into different concentrations including 10%, 6%, 3%, 1% and 0.5% (n=30). Cell-free DNA collected from pregnant women (n=13) whose fetuses were confirmed free of FGFR3 mutation by Sanger sequencing served as negative control . Then NGS was carried out to detect the fetal mutant allele in these samples. Sensitivity, specificity, positive predictive value, negative predictive value were calculated to evaluate the test performance.Results When the fetal gDNA concentrations were 10%, 6%, 3%, 1% and 0.5%,the detection rates were 6/6, 6/6, 6/6, 3/6 and 1/6, respectively. NGS had a sensitivity of 100%(95%CI: 81.5%-99.9%)when the fetal genome DNA concentration was equal to or more than 3%. There was no positive result in the negative controls and the specificity of NGS was 100%(95%CI: 75.3%-100%). The positive predictive value and negative predictive value were 100%(95%CI: 81.5%-100%) and 100%(95%CI: 75.3%-100%), respectively. Conclusion NGS has a high accuracy in detecting FGFR3 mutation when the concentration of fetal gDNA is equal to or more than 3% , highlighting its promising value in developing non-invasive prenatal test for monogenic disorders, especially for the denovo and paternal inherited diseases.关键词
新一代测序技术/无创产前检测/胎儿游离DNA/软骨发育不全/FGFR3基因Key words
next-generation sequencing/non-invasive prenatal test/cell-free fetal DNA/achondroplasia/FGFR3 gene分类
医药卫生引用本文复制引用
任远,高雅,卢彦平,赵佳,李芮冰,刘弘泰,姜淑芳,谢一帆,周红辉..新一代测序技术无创产前检测胎儿FGFR3基因突变[J].解放军医学院学报,2017,38(1):14-18,21,6.
