Wright Dale, Carey Louise, Battersby Siobhan, Nguyen Thuy, Clarke Melanie, Nash Benjamin, Gulesserian Elee, Cross Jill, Darmanian Artur
Department of Cytogenetics, Sydney Genome Diagnostics, The Children's Hospital at Westmead , Westmead, Australia .
Genet Test Mol Biomarkers. 2016 Dec;20(12):791-798. doi: 10.1089/gtmb.2016.0117. Epub 2016 Sep 30.
Validation of a chromosomal microarray for improved prenatal diagnosis for chromosomal abnormalities among high-risk pregnancies.
A cohort of 213 pregnancies was investigated by chromosomal microarray and the results were compared with quantitative fluorescent polymerase chain reaction (QF-PCR), karyotype, and 850K single-nucleotide polymorphism microarray results. The detection limit of mosaicism was determined by assaying different trisomy mosaic constructs down to ∼12%. Imprecision estimates from replicates of mean log ratio values for a 200 kb deletion and 400 kb duplication were determined by evaluating the coefficient of variation (CV%).
Excluding pregnancies with aneuploidy, the chromosomal microarray detected 19/213 (8.9%) pregnancies with copy number abnormalities. These were classified as pathogenic in 11/213 (5.2%) cases, as variants of uncertain significance in 4/213 (1.9%) cases, and as likely benign in 4/213 (1.9%) cases. In 15/213 (7.0%) pregnancies, these abnormalities were not detectable by karyotype. Importantly, 8/11 (72.7%) of the pathogenic abnormalities detected by chromosomal microarray were only detectable by this modality. There were no false-positive results and only eight false-negative results. The chromosomal microarray showed excellent sensitivity (96.2%) and specificity (100.0%). The lower detection limit for mosaicism was ∼12%. Imprecision for the 0.2 Mb deletion (11.6 CV%) and 0.4 Mb duplication (5.9 CV%) was very low.
This chromosomal microarray showed excellent diagnostic performance with improved detection rates compared to karyotyping for prenatal diagnosis of clinically relevant fetal chromosomal abnormalities.
验证染色体微阵列技术在高危妊娠中改善染色体异常产前诊断的效果。
对213例妊娠进行染色体微阵列检测，并将结果与定量荧光聚合酶链反应（QF-PCR）、核型分析及850K单核苷酸多态性微阵列结果进行比较。通过检测低至约12%的不同三体镶嵌构建体来确定镶嵌现象的检测限。通过评估变异系数（CV%）来确定200 kb缺失和400 kb重复的平均对数比值值重复检测的不精密度估计值。
排除非整倍体妊娠，染色体微阵列检测到19/213（8.9%）例妊娠存在拷贝数异常。其中11/213（5.2%）例被分类为致病性异常，4/213（1.9%）例为意义不明确的变异，4/213（1.9%）例可能为良性异常。在15/213（7.0%）例妊娠中，核型分析未检测到这些异常。重要的是，染色体微阵列检测到的8/11（72.7%）例致病性异常仅通过该方法可检测到。无假阳性结果，仅8例假阴性结果。染色体微阵列显示出极佳的敏感性（96.2%）和特异性（100.0%）。镶嵌现象的较低检测限约为12%。0.2 Mb缺失（CV%为11.6）和0.4 Mb重复（CV%为5.9）的不精密度非常低。
与核型分析相比，这种染色体微阵列在临床相关胎儿染色体异常的产前诊断中显示出优异的诊断性能，检测率有所提高。
