比较基因组杂交微阵列技术在唐氏综合征血清学筛查结果异常孕妇产前诊断中的应用

Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down’s Syndrome

目的探讨比较基因组杂交微阵列(array-based comparative genomic hybridization,a-CGH)技术在唐氏综合征血清学筛查(简称唐筛)结果异常孕妇产前诊断中的应用。方法选取单纯因唐筛结果异常、并行羊膜腔穿刺取羊水标本进行产前检查诊断的单胎孕妇3578例为研究对象,将其分为3组:唐筛高风险组(2624例)、唐筛临界风险组(662例)及唐筛单项中位数的倍数(multiples of median,MoM)值异常组(292例)。采用CGX^(TM)(8×60K)芯片对其羊水进行a-CGH检测,并采用Genoglyphix■软件进行分析。结果3578例羊水标本中,a-CGH分析共检出染色体异常121例,总体异常检出率为3.38%,其中非整倍体60例,占49.59%;致病性拷贝数变异51例,占42.15%;可能致病拷贝数变异10例,占8.26%。检出不明意义拷贝数变异37例,占总数的1.03%。唐筛高风险组、唐筛临界风险组及唐筛单项MoM值异常组的总体异常检出率分别为3.54%(93/2624)、2.87%(19/662)及3.08%(9/292);致病性和可能致病拷贝数变异检出率分别为1.64%(43/2624)、1.81%(12/662)及2.05%(6/292);18-及21-三体检出率分别为1.37%(36/2624)、0.76%(5/662)及0.34%(1/292),差异均无统计学意义(P>0.05)。a-CGH漏检染色体异常1例,荧光原位杂交诊断为X(51)/XYY(49)。结论a-CGH技术在唐筛结果异常的孕妇产前诊断中不仅可以检测非整倍体异常,还可以检出微缺失/微重复综合征等染色体拷贝数变异。

Objective To explore the application of array-based comparative genomic hybridization(a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down’s syndrome(DS).Methods A total of 3578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected.The samples were categorized into 3 groups,2624 in the high-risk group,662 in the borderline-risk group,and 292 in the abnormal multiple of median(MoM)group.a-CGH was performed on the Agilent CGX^(TM)(8×60 K)platform and the data were analyzed by the Genoglyphix■software.Results The overall detection rate of chromosomal abnormalities was 3.38%(121/3578).Among the chromosomal abnormalities,49.59%(60/121)was aneuploidies,42.15%(51/121)was pathogenic copy number variants(pCNVs),and 8.26%(10/121)was likely pathogenic CNVs(lpCNVs).The detection rate of copy number variant of uncertain significance(VUS)was 1.03%(37/3578).In the high-risk,the borderline-risk and the abnormal MoM groups,the detection rate of chromosomal abnormalities was 3.54%(93/2624),2.87%(19/662)and 3.08%(9/292),respectively;the detection rate of p/lp CNVs was 1.64%(43/2624),1.81%(12/662)and 2.05%(6/292),respectively;the detection rate of trisomy 21 and trisomy 18 was 1.37%(36/2624),0.76%(5/662)and 0.34%(1/292)in the three groups,respectively.There were no significant differences in all the detection rate among these groups(P>0.05).One sample with X(51)/XYY(49)confirmed by fluorescence in situ hybridization(FISH)was misdiagnosed by a-CGH.Conclusion Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS.It can also be used to detect CNVs of microdeletion/microduplication syndromes.