Department of Medical Genetics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, 610041, China.
BMC Pregnancy Childbirth. 2023 Aug 19;23(1):593. doi: 10.1186/s12884-023-05921-x.
Standard noninvasive prenatal screening(NIPS) is an accurate and reliable method to screen for common chromosome aneuploidies, such as trisomy 21, 18 and 13. Extended NIPS has been used in clinic for not only aneuploidies but also copy number variants(CNVs). Here we aim to define the range of chromosomal abnormalities that should be able to identify by NIPS in order to be an efficient extended screening test for chromosomal abnormalities.
A prospective study was conducted, involving pregnant women without fetal sonographic structural abnormalities who underwent amniocentesis. Prenatal samples were analyzed using copy number variation sequencing(CNV-seq) to identify fetal chromosomal abnormalities.
Of 28,469 pregnancies included 1,022 (3.59%) were identified with clinically significant fetal chromosome abnormalities, including 587 aneuploidies (2.06%) and 435 (1.53%) pathogenic (P) / likely pathogenic (LP) CNVs. P/LP CNVs were found in all chromosomes, but the distribution was not uniform. Among them, P/LP CNVs in chromosomes 16, 22, and X exhibited the highest frequencies. In addition, P/LP CNVs were most common on distal ends of the chromosomes and in low copy repeat regions. Recurrent microdeletion/microduplication syndromes (MMS) accounted for 40.69% of total P/LP CNVs. The size of most P/LP CNVs (77.47%) was < 3 Mb.
In addition to aneuploidies, the scope of extended NIPS should include the currently known P/LP CNVs, especially the regions with recurrent MMS loci, distal ends of the chromosomes, and low copy repeat regions. To be effective detection should include CNVs of < 3 Mb. Meanwhile, sufficient preclinical validation is still needed to ensure the clinical effect of extended NIPS.
标准的无创产前筛查（NIPS）是一种准确可靠的方法，可用于筛查常见的染色体非整倍体，如 21 三体、18 三体和 13 三体。扩展 NIPS 不仅用于非整倍体，还用于拷贝数变异（CNV）。在这里，我们旨在确定 NIPS 能够识别的染色体异常范围，以便成为一种有效的染色体异常扩展筛查测试。
进行了一项前瞻性研究，涉及接受羊膜穿刺术的无胎儿超声结构异常的孕妇。使用拷贝数变异测序（CNV-seq）对产前样本进行分析，以识别胎儿染色体异常。
在 28469 例妊娠中，有 1022 例（3.59%）被确定为具有临床意义的胎儿染色体异常，包括 587 例非整倍体（2.06%）和 435 例致病性（P）/可能致病性（LP）CNV。所有染色体均发现 P/LP CNV，但分布不均匀。其中，染色体 16、22 和 X 上的 P/LP CNV 频率最高。此外，P/LP CNV 最常见于染色体的远端和低拷贝重复区域。反复出现的微缺失/微重复综合征（MMS）占总 P/LP CNV 的 40.69%。大多数 P/LP CNV 的大小（77.47%）<3 Mb。
除了非整倍体外，扩展 NIPS 的范围还应包括目前已知的 P/LP CNV，特别是具有反复出现的 MMS 基因座、染色体远端和低拷贝重复区域的区域。有效的检测应包括<3 Mb 的 CNV。同时，仍需要充分的临床前验证，以确保扩展 NIPS 的临床效果。
