扩展型无创性产前检测在检测染色体非整倍体和微缺失/微重复中的临床应用价值评估。
Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication.
机构信息
Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Maternal and Child Health Hospital of Henan Province, No. 7 Front Kangfu Street, Er'qi District, Zhengzhou, 450052, China.
Department of Medical Research Center, The Third Affiliated Hospital of Zhengzhou University, Maternal and Child Health Hospital of Henan Province, Zhengzhou, 450052, China.
出版信息
Eur J Med Res. 2023 Aug 30;28(1):304. doi: 10.1186/s40001-023-01285-2.
BACKGROUND
With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS).
METHODS
A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed.
RESULTS
Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin.
CONCLUSION
The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments < 5 M is low, and the missed detection rate is high. Additionally, confined placental mosaicism and foetal mosaicism are the key factors causing false negatives in NIPT-PLUS, while maternal chromosomal abnormalities and confined placental mosaicism are key contributors to false positives, so appropriate genetic counselling is especially important for pregnant women before and after NIPT-PLUS testing.
背景
随着全基因组测序技术的发展，非侵入性产前检测（NIPT）已逐渐应用于筛查传统核型分析无法检测到的染色体微缺失和微重复。然而，在 NIPT 中，会出现一些假阳性和假阴性。本研究旨在探讨扩展 NIPT（NIPT-PLUS）在检测染色体非整倍体和微缺失/微重复综合征（MMS）中的适用性。
方法
从接受染色体微阵列分析（CMA）产前诊断检测（羊膜穿刺术或绒毛活检）的 452 例妊娠中，筛选出外周血样本进行 NIPT-PLUS 检测。对两项检测结果进行比较和分析。
结果
在 452 例中，335 例（74.12%）CMA 结果阳性，117 例（25.88%）无异常。通过 CMA 和 NIPT-PLUS 共检测到 86 例 21、18 和 13 三体及性染色体非整倍体（SCA），检出率为 96.51%（83/86）。其中，T18、T13；47，XXY；47，XXX 和 47 XYY 的检出率为 100%，T21 和 45 XO 的检出率为 96.55%和 90%。罕见染色体三体（RAT）的检测灵敏度为 80%（4/5）。NIPT-PLUS 对染色体非整倍体 T21、T18 和 T13 及 SCA 和 RAT 的阳性预测值分别为 90.32%、87.50%、25.00%、88.89%和 50%。通过 CMA 共检测到 249 例（74.32%）染色体 MMS。NIPT-PLUS 的检出率为 63.86%（159/249），漏诊 90 例（36.14%）。MMS 片段越大，NIPT-PLUS 的检测灵敏度越高。此外，大多数小片段来源于母体。
结论
CMA 和 NIPT-PLUS 技术的比较表明，NIPT-PLUS 对检测染色体非整倍体和片段>5M 的染色体拷贝数变异（CNV）具有较高的灵敏度。然而，片段<5M 的 CNV 检测灵敏度较低，漏诊率较高。此外，胎盘局限性嵌合体和胎儿局限性嵌合体是导致 NIPT-PLUS 假阴性的关键因素，而母体染色体异常和胎盘局限性嵌合体是导致假阳性的关键因素，因此，在进行 NIPT-PLUS 检测前后，对孕妇进行适当的遗传咨询尤为重要。
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