利用染色体芯片分析和全外显子测序对胎儿右主动脉弓进行产前诊断：一项中国单中心回顾性研究。

IF 1.3 4区生物学 Q4 GENETICS & HEREDITY

Molecular Cytogenetics Pub Date : 2024-09-27 DOI:10.1186/s13039-024-00691-3

Lu Zhang, Ruibin Huang, Hang Zhou, Xiaomei Lin, Fei Guo, Xiangyi Jing, Yongling Zhang, Fucheng Li, Fatao Li, Qiuxia Yu, Dan Wang, Guilan Chen, Fang Fu, Min Pan, Jin Han, Dongzhi Li, Ru Li

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引用次数: 0

摘要

背景：右主动脉弓（RAA）是一种常见的先天性主动脉弓畸形。患有 RAA 的胎儿出生后通常都能获得良好的预后。然而，染色体异常和遗传综合征提示这些患者预后不良。迄今为止，基于传统的遗传学技术，大多数 RAA 患者的潜在遗传病因仍未确定，而孤立 RAA 胎儿是否应转诊至 CMA 仍是一个争论不休的问题。我们的研究旨在通过染色体微阵列分析（CMA）和全外显子组测序（WES）研究右主动脉弓（RAA）胎儿的遗传学病因，并评估 CMA 对胎儿孤立型 RAA 的疗效：在这153个胎儿中，99个（64.7%）为孤立性RAA，54个（35.3%）为非孤立性RAA；25.5%（39/153）为额外的心内畸形（ICA），19.0%（29/153）为心外畸形（ECA）。法洛四联症（10 例）和持续性左上腔静脉（11 例）分别是最常见的 ICA 和 ECA。CMA 在 14 个病例（9.2%）中检测到 15 个具有临床意义的拷贝数变异（CNV）；22q11.21 微缺失是最常见的致病性 CNV（7.8%）。非孤立 RAA 组和 RAA 伴 ICA 组的染色体异常率高于孤立 RAA 组（16.7% vs. 5.1%；20% vs. 5.1%，均 p <0.05）。在进一步接受WES检查的5个病例中，首次报告了产前MTOR基因的诊断性变异（c.7255G > A，从头开始），扩展了Smith-Kingsmore综合征（OMIM：616638）的产前表现；发现了STAG2基因的临床相关变异c.3407A > T，遗传自健康母亲。此外，非分离 RAA 组的早产率和终止妊娠率均高于分离 RAA 组（11.1% 对 1.0%；37.0% 对 2.0%，均 p <0.01）：我们证明，CMA 和 WES 是诊断胎儿 RAA（尤其是非分离型 RAA）的有用工具，所有 RAA 胎儿都应转诊进行 CMA 检查。这些数据可能有助于胎儿 RAA 的产前诊断和产前咨询。

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Prenatal diagnosis in fetal right aortic arch using chromosomal microarray analysis and whole exome sequencing: a Chinese single-center retrospective study.

Background: Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA.

Results: Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith-Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01).

Conclusions: We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.

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来源期刊

Molecular Cytogenetics GENETICS & HEREDITY-

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Cytogenetics encompasses all aspects of chromosome biology and the application of molecular cytogenetic techniques in all areas of biology and medicine, including structural and functional organization of the chromosome and nucleus, genome variation, expression and evolution, chromosome abnormalities and genomic variations in medical genetics and tumor genetics. Molecular Cytogenetics primarily defines a large set of the techniques that operate either with the entire genome or with specific targeted DNA sequences. Topical areas include, but are not limited to: -Structural and functional organization of chromosome and nucleus- Genome variation, expression and evolution- Animal and plant molecular cytogenetics and genomics- Chromosome abnormalities and genomic variations in clinical genetics- Applications in preimplantation, pre- and post-natal diagnosis- Applications in the central nervous system, cancer and haematology research- Previously unreported applications of molecular cytogenetic techniques- Development of new techniques or significant enhancements to established techniques. This journal is a source for numerous scientists all over the world, who wish to improve or introduce molecular cytogenetic techniques into their practice.