【摘要】 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3 578例为研究对象,将其分为3组:唐筛高风险组(2 624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?(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 3 578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%(93/2 624)、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%(43/2 624)、1.81%(12/662)及2.05%(6/292);18-及21-三体检出率分别为1.37%(36/2 624)、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。更多还原

【Abstract】 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 3 578 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, 2 624 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?(8×60 K) platform and the data were analyzed by the Genoglyphix? software. Results The overall detection rate of chromosomal abnormalities was 3.38%(121/3 578).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%(37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54%(93/2 624), 2.87%(19/662) and 3.08%(9/292),respectively; the detection rate of p/lp CNVs was 1.64%(43/2 624), 1.81%(12/662) and 2.05%(6/292), respectively;the detection rate of trisomy 21 and trisomy 18 was 1.37%(36/2 624), 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.更多还原