无创产前筛查检测胎儿染色体缺失或重复的应用价值分析
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摘要
目的探讨无创产前检测(NIPT)在胎儿染色体微缺失/微重复检测中的应用价值。方法对26例NIPT提示存在染色体缺失和/或重复的孕妇行羊膜腔穿刺术,进行染色体核型分析及低覆盖度全基因组测序技术检测拷贝数变异。结果NIPT提示存在染色体信号异常的26例孕妇中,经染色体核型分析及拷贝数变异检测确诊11例,符合率42.31%(11/26)。其中18例NIPT明确提示存在染色体的缺失或重复,经验证后确诊9例,符合率50.00%(9/18),且缺失和/或重复的位置及片段大小与NIPT结果基本一致。结论将NIPT的筛查范围扩大到胎儿全基因组拷贝数变异的检测,从技术上来说是可行的。
Objective:To investigate the clinical application value of noninvasive prenatal testing for detection of fetal subchromosome abnormalities. Methods:Amniotic fluid amniocentesis and karyotype analysis and CNV sequencing were sampled from 26 pregnant women whose NIPT results were abnormal. Results:The sensitivity was determined to be 42.31% in testing26 samples.9 cases that detected genomewide gains and losses of chromosomal material were confirmed by CNV sequencing.Conclusion:Noninvasive prenatal testing can be expanded into the detection of subchromosomal copy number variations. The limit of detection for CNV is constrained by fetal fraction,microdeletion/microduplication size and coverage.
Objective:To investigate the clinical application value of noninvasive prenatal testing for detection of fetal subchromosome abnormalities. Methods:Amniotic fluid amniocentesis and karyotype analysis and CNV sequencing were sampled from 26 pregnant women whose NIPT results were abnormal. Results:The sensitivity was determined to be 42.31% in testing26 samples.9 cases that detected genomewide gains and losses of chromosomal material were confirmed by CNV sequencing.Conclusion:Noninvasive prenatal testing can be expanded into the detection of subchromosomal copy number variations. The limit of detection for CNV is constrained by fetal fraction,microdeletion/microduplication size and coverage.
引文
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[8]Schlutter JM,Hatt L,Bach C,et al. The cell-free fetal DNA fraction in maternal blood decreases after physical activity[J].Prenat Diagn,2014,34(4):341-344.
[9]Li R, Wan J,Zhang Y,et al.Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies[J].Ultrasound Obstet Gynecol,2016,47(1):53-7.
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[11]LoKK,KarampetsouE,BoustredC,etal.Limited ClinicalUtilityofnon-invasivePrenatalTestingfor Subchromosomal Abnormalities[J]. Am J Hum Genet, 2016,98(1):34-44.
[12]Helgeson J, Wardrop J, Boomer T,et al. Clinical outcome of subchromosomal events detected by whole-genome noninvasive prenatal testing[J]. Prenat Diagn, 2015,35(10):999-1004.
[13]Benn P, Borell A, Chiu R,et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis[J]. Prenat Diagn,2015,35(8):725-734.
[2]Redon R,Ishikawa S,Fitch KR,et al. Global variation in copy number in the human genome[J].Nature,2006,444(7118):444-445.
[3]Peters D,Chu T,Yatsenko SA,et a1. Noninvasive prenatal diagnosis of a fetal microdeletion syndrome[J].N Engl J Med,2011,365:1847-1848.
[4]JensenT,DzakulaZ,DeciuC,et al. Detectionof microdeletion22q11.2 in a fetus by next-generation sequencing of maternal plasma[J].ClinChem,2012,58(7):1148-1151.
[5]Srinivasan A1, Bianchi DW, Huang H,et al. Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma[J].Am J Hum Genet, 2013,92(2):167-176.
[6]ZhaoC,TynanJ,EhrichM,eta1.Detectionoffetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma[J].Clin Chem,2015,61:608-616.
[7]Lo YM,Corbetta N,Chamberlain PF,et a1.Presence of fetal DNA in maternal plasma and serum[J].Lancet,1997,350:485-487.
[8]Schlutter JM,Hatt L,Bach C,et al. The cell-free fetal DNA fraction in maternal blood decreases after physical activity[J].Prenat Diagn,2014,34(4):341-344.
[9]Li R, Wan J,Zhang Y,et al.Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies[J].Ultrasound Obstet Gynecol,2016,47(1):53-7.
[10]Lefkowitz RB,Tynan JA,Liu T,et al.Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants.[J]. Am J Obstet Gynecol,2016,215(2):227.e1-227.e16.
[11]LoKK,KarampetsouE,BoustredC,etal.Limited ClinicalUtilityofnon-invasivePrenatalTestingfor Subchromosomal Abnormalities[J]. Am J Hum Genet, 2016,98(1):34-44.
[12]Helgeson J, Wardrop J, Boomer T,et al. Clinical outcome of subchromosomal events detected by whole-genome noninvasive prenatal testing[J]. Prenat Diagn, 2015,35(10):999-1004.
[13]Benn P, Borell A, Chiu R,et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis[J]. Prenat Diagn,2015,35(8):725-734.