每次怀孕都要进行外显子组测序?结构正常胎儿的三组外显子测序结果。

IF 2.7 2区 医学 Q2 GENETICS & HEREDITY
Prenatal Diagnosis Pub Date : 2025-03-01 Epub Date: 2024-05-12 DOI:10.1002/pd.6585
Michal Levy, Shira Lifshitz, Mirela Goldenberg-Fumanov, Lily Bazak, Rayna Joy Goldstein, Uri Hamiel, Rachel Berger, Shlomo Lipitz, Idit Maya, Mordechai Shohat
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引用次数: 0

摘要

研究目的本研究旨在评估产前外显子测序(pES)在非近亲结婚夫妇的低风险妊娠和明显正常胎儿中具有临床意义结果的检出率:方法:对一个中心在 2020 年 1 月至 2023 年 9 月期间进行的 pES 进行了回顾性分析。提供了遗传咨询,并获得了详细的病史。排除了因重大超声异常、超声软标记物、母体生化筛查异常或家族史提示单基因疾病而导致的高危妊娠,以及染色体微阵列结果为致病和可能致病(P/LP)的病例。外显子组分析侧重于与孟德尔遗传疾病相关的 2100 个基因。变异分析和分类遵循美国医学遗传学和基因组学学院(ACMG)指南:在进行的 1825 例 pES 中,1020 例低风险病例发现 28 个胎儿(2.7%)存在具有潜在临床意义的变异,表明存在已知的单基因疾病,主要是新生显性变异(64%)。在这 28 个病例中,9 个胎儿(0.9%)可能出现严重表型,包括寿命缩短和智力残疾,另外 12 个胎儿可能出现较轻的表型。根据 ACMG 标准,有 7 例胎儿存在意义不确定的变异(VUS),倾向于 LP,占整个队列的 0.7%。队列中的 1020 个病例中有 13 例(1.2%)选择终止妊娠,其中重度表型组 7/9 例,轻度表型组 2/12 例,VUS 组 4/7 例:2.7%的检出率凸显了pES在低风险妊娠中的重要作用。结论:2.7% 的检出率凸显了 pES 在低风险妊娠中的重要作用,但需要进行严格的分析,并在检测前后提供全面的遗传咨询。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exome sequencing in every pregnancy? Results of trio exome sequencing in structurally normal fetuses.

Objective: This study aimed to assess the detection rate of clinically significant results of prenatal exome sequencing (pES) in low-risk pregnancies and apparently normal fetuses in non-consanguineous couples.

Methods: A retrospective analysis of pES conducted at a single center from January 2020 to September 2023 was performed. Genetic counseling was provided, and detailed medical histories were obtained. High-risk pregnancies were excluded due to major ultrasound anomalies, sonographic soft markers, abnormal maternal biochemical screening, or family history suggestive of monogenic diseases as well as cases with pathogenic and likely pathogenic (P/LP) chromosomal microarray results. Exome analysis focused on ∼2100 genes associated with Mendelian genetic disorders. Variant analysis and classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines.

Results: Among 1825 pES conducted, 1020 low-risk cases revealed 28 fetuses (2.7%) with potentially clinically significant variants indicating known monogenic diseases, primarily de novo dominant variants (64%). Among these 28 cases, 9 fetuses (0.9%) had the potential for severe phenotypes, including shortened lifespan and intellectual disability, and another 12 had the potential for milder phenotypes. Seven cases were reported with variants of uncertain significance (VUS) that, according to the ACMG criteria, leaned toward LP, constituting 0.7% of the entire cohort. Termination of pregnancy was elected in 13 out of 1020 cases (1.2%) in the cohort, including 7/9 in the severe phenotypes group, 2/12 in the milder phenotype group, and 4/7 in the VUS group.

Conclusion: The 2.7% detection rate highlights the significant contribution of pES in low-risk pregnancies. However, it necessitates rigorous analysis, and comprehensive genetic counseling before and after testing.

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来源期刊
Prenatal Diagnosis
Prenatal Diagnosis 医学-妇产科学
CiteScore
5.80
自引率
13.30%
发文量
204
审稿时长
2 months
期刊介绍: Prenatal Diagnosis welcomes submissions in all aspects of prenatal diagnosis with a particular focus on areas in which molecular biology and genetics interface with prenatal care and therapy, encompassing: all aspects of fetal imaging, including sonography and magnetic resonance imaging; prenatal cytogenetics, including molecular studies and array CGH; prenatal screening studies; fetal cells and cell-free nucleic acids in maternal blood and other fluids; preimplantation genetic diagnosis (PGD); prenatal diagnosis of single gene disorders, including metabolic disorders; fetal therapy; fetal and placental development and pathology; development and evaluation of laboratory services for prenatal diagnosis; psychosocial, legal, ethical and economic aspects of prenatal diagnosis; prenatal genetic counseling
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