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 ™ (8×60K) 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.
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%（43/2624）、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。
Keywords: Array-based comparative genomic hybridization; Chromosome microarray analysis; Copy number variants; Prenatal diagnosis; Serological prenatal screening.
Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).