Performance of non-invasive prenatal screening for 15q11q13 copy number variations in a cohort of 90,693 pregnancies.

IF 3 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2026-10-09 eCollection Date: 2026-01-01 DOI:10.3389/fgene.2026.1937108

Diyu Chen, Liang Hu, Hongyan Niu, Zhenming Li, Shuxian Zeng, Xiaoyi Cong, Pingnan Sun, Weiqiang Liu

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引用次数: 0

Abstract

Background: Deletions and duplications within the 15q11q13 chromosomal region are associated with Prader-Willi syndrome, Angelman syndrome, and 15q11q13 duplication syndrome. However, prenatal ultrasound findings were unremarkable in the majority of affected fetuses. The aim of this study was to evaluate the efficacy of non-invasive prenatal screening (NIPS) in identifying these syndromes in 90,693 pregnancies within the general population.

Methods: We retrospectively analyzed 90,693 pregnant women who underwent NIPS at Longgang Maternal and Child Health Hospital in Shenzhen from November 2022 to January 2026. For high-risk 15q11q13 copy number variations (CNVs) identified, we performed chromosomal microarray analysis (CMA) on amniotic fluid, followed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) or further CMA to determine the CNVs' genetic origin, with subsequent follow-up.

Results: NIPS screening identified 4 high-risk cases for 15q11q13 deletion and 7 for duplication. Among the deletion cases, 3 were confirmed by CMA to have a 5-6 Mb deletion (2 maternal, 1 unverified), while 1 declined further testing. For duplication, 6 underwent amniocentesis, with CMA confirming 5 cases (2 maternal, 2 paternal, 1 unverified), 1 normal result, and 1 declined further testing. Of the 8 true-positive cases, 7 had normal ultrasounds, but 1 fetus with duplication exhibited growth retardation. Pregnancy outcomes included 6 terminations, one delivery with paternal duplication showing mild language delay at nearly 2 years, and another with maternal duplication lost to follow-up.

Conclusion: NIPS can effectively detect CNVs at the 15q11q13 locus with a high positive predictive value, but its sensitivity, specificity, negative predictive value, and false-negative rate could not be determined in this study due to the lack of confirmatory testing in low-risk cases. Invasive prenatal diagnosis remains essential for validation.

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90,693例妊娠队列中15q11q13拷贝数变异的无创产前筛查

背景：15q11q13染色体区域的缺失和重复与Prader-Willi综合征、Angelman综合征和15q11q13重复综合征有关。然而，产前超声结果在大多数受影响的胎儿是不显著的。本研究的目的是评估无创产前筛查（NIPS）在90,693例普通人群中识别这些综合征的有效性。方法：回顾性分析2022年11月至2026年1月在深圳龙岗妇幼保健院接受NIPS治疗的90693例孕妇。对于鉴定出的高风险15q11q13拷贝数变异（CNVs），我们对羊水进行了染色体微阵列分析（CMA），然后进行甲基化特异性多重结扎依赖探针扩增（MS-MLPA）或进一步的CMA，以确定CNVs的遗传起源，并进行随访。结果：NIPS筛查发现4例15q11q13缺失高危病例和7例重复高危病例。在缺失病例中，3例经CMA确认有5-6 Mb缺失（2例母系，1例未经证实），1例拒绝进一步检测。对于重复，6例进行羊膜穿刺术，CMA确认5例（2例母系，2例父系，1例未经证实），1例结果正常，1例拒绝进一步检测。在8例真阳性病例中，7例超声检查正常，但1例双胎胎儿表现为发育迟缓。妊娠结局包括6例终止妊娠，1例父系重复分娩表现出近2年的轻度语言迟缓，另1例母系重复分娩未能随访。结论：NIPS能有效检测15q11q13位点的CNVs，阳性预测值高，但由于缺乏对低危病例的确证性检测，本研究无法确定NIPS的敏感性、特异性、阴性预测值和假阴性率。侵入性产前诊断仍然是必要的验证。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.