NIPT高风险者羊水染色体核型及高通量测序全基因组拷贝变异数检测结果分析
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摘要
目的分析无创产前检测(Non-invasive prenatal testing NIPT)高风险者的染色体检测结果及高通量测序全基因组拷贝变异数检测(NGS-CNVs)结果,探讨NIPT和染色体核型分析及NGS-CNVs在产前诊断中的联合应用价值。方法对73例NIPT提示阳性的孕妇行羊膜腔穿刺术,细胞培养染色体核型分析以确定胎儿染色体核型,其中45例NIPT高风险者同时行NGS-CNVs。结果 73例NIPT高风险对21三体的阳性预测值最高(85.71%),然后依次为18三体(71.43%),性染色体数目异常(65.63%),13三体(33.33%),其他染色体异常(25%)。6例NGS-CNVs与核型检测不一致,染色体核型2例9号倒位和1例平衡易位NGS-CNVs未检出;NGS-CNVs显示3例微缺失/微重复而染色体核型未检出,其中可能致病性拷贝数变异(CNVs)1例,临床意义不明的CNVs1例,多态性CNVs1例。结论 NIPT是一种有效的且无创的产前筛查手段,联合染色体核型分析及NGS-CNVs既可以检出染色体倒位和平衡易位又可以覆盖染色体微缺失或微重复,对产前诊断意义重大。
Objective:To analyze the results of chromosome detection and high-throughput sequencing of whole genome copy variation detection(NGS-CNVs)in high-risk patients with non-invasive prenatal testing(NIPT),and to explore the combined value of NIPT and karyotype analysis and NGS-CNVs in prenatal diagnosis. Methods:A total of 73 pregnant women with positive NIPT were treated with amniocentesis,and then karyotype analysis of cell culture was performed to determine the karyotype of the fetus. 45 of the high-risk NIPT patients voluntarily tested CNVs simultaneously. Results:73 patients with NIPT had the highest positive predictive value for the trisomy 21(85.71%),followed by 18 trisomy(71.43%),sex chromosomes number abnormalities(65.63%),13 trisomy(33.33%),other chromosomal abnormalities(25%). Six cases of NGS-CNVs were inconsistent with karyotype detection,karyotype 2 cases of 9 th inversion and 1 case of balanced translocation NGS-CNVs were not detected;NGS-CNVs showed 3 cases of microdeletion/microrepetition and karyotype was not detected Among them,there were 1 case of pathogenic copy number variation(CNVs),1 case of CNVs with unclear clinical significance,and 1 case of benign CNVs. Conclusion:NIPT is an effective and non-invasive prenatal screening method,combined karyotype analysis and NGS-CNVs can detect both chromosomal inversions and balanced translocations,as well as chromosomal microdeletions or microduplications,which is of great significance to prenatal diagnosis.
Objective:To analyze the results of chromosome detection and high-throughput sequencing of whole genome copy variation detection(NGS-CNVs)in high-risk patients with non-invasive prenatal testing(NIPT),and to explore the combined value of NIPT and karyotype analysis and NGS-CNVs in prenatal diagnosis. Methods:A total of 73 pregnant women with positive NIPT were treated with amniocentesis,and then karyotype analysis of cell culture was performed to determine the karyotype of the fetus. 45 of the high-risk NIPT patients voluntarily tested CNVs simultaneously. Results:73 patients with NIPT had the highest positive predictive value for the trisomy 21(85.71%),followed by 18 trisomy(71.43%),sex chromosomes number abnormalities(65.63%),13 trisomy(33.33%),other chromosomal abnormalities(25%). Six cases of NGS-CNVs were inconsistent with karyotype detection,karyotype 2 cases of 9 th inversion and 1 case of balanced translocation NGS-CNVs were not detected;NGS-CNVs showed 3 cases of microdeletion/microrepetition and karyotype was not detected Among them,there were 1 case of pathogenic copy number variation(CNVs),1 case of CNVs with unclear clinical significance,and 1 case of benign CNVs. Conclusion:NIPT is an effective and non-invasive prenatal screening method,combined karyotype analysis and NGS-CNVs can detect both chromosomal inversions and balanced translocations,as well as chromosomal microdeletions or microduplications,which is of great significance to prenatal diagnosis.
引文
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[5]胡祝明,朱海波,李琳琳等.产前无创DNA筛查高风险孕妇羊水穿刺诊断符合率分析[J].中华医学遗传学杂志,2018,35(2):304-306.
[6]Mazloom AR1,D?akula?,Oeth P,et al.Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma[J].Prenat Diagn,2013,33(6):591-597.
[7]周静,蒋涛,李璃,等.羊水细胞染色体核型分析和微阵列比较基因组杂交技术验证无创产前检测的临床意义[J].实用妇产科杂志.2015,31(4):292-295.
[8]Hartwig TS,Ambye L,S?rensen S,et al.Discordant non-invasive prenatal testing(NIPT)-a systematic review[J].Prenat Diagn,2017,37(6):527-39.
[9]Lau TK,Cheung SW,Lo PS,et al.Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage wholegenome sequencing of maternal plasma DNA:review of1982 consecutive cases in a single center[J].Ultrasound Obstet Gynecol,2014 Mar,43(3):254-64.
[2]Hui L,Teoh M,da Silva Costa F,et al.Clinical implementation of cell-free DNA-based aneuploidy screening:perspectives from a national audit[J].Ultrasond Obstet Gynecol,2015,45(1):10-15.
[3]Palomaki GE,Deciu C,Kloza EM,et al.DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome:an international collaborative study[J].Genet Med,2012,14(3):296-305.
[4]蓝慧娟,邵聪文,王辉林等.95例NIPT高风险者羊水染色体检测结果分析[J].国际检验医学杂志,2017,38(13):1749-1753.
[5]胡祝明,朱海波,李琳琳等.产前无创DNA筛查高风险孕妇羊水穿刺诊断符合率分析[J].中华医学遗传学杂志,2018,35(2):304-306.
[6]Mazloom AR1,D?akula?,Oeth P,et al.Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma[J].Prenat Diagn,2013,33(6):591-597.
[7]周静,蒋涛,李璃,等.羊水细胞染色体核型分析和微阵列比较基因组杂交技术验证无创产前检测的临床意义[J].实用妇产科杂志.2015,31(4):292-295.
[8]Hartwig TS,Ambye L,S?rensen S,et al.Discordant non-invasive prenatal testing(NIPT)-a systematic review[J].Prenat Diagn,2017,37(6):527-39.
[9]Lau TK,Cheung SW,Lo PS,et al.Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage wholegenome sequencing of maternal plasma DNA:review of1982 consecutive cases in a single center[J].Ultrasound Obstet Gynecol,2014 Mar,43(3):254-64.