Exome sequencing and prenatal skeletal abnormalities: comprehensive review and meta-analysis and way forward.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-06-11 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1502538

Mengting Jiang, Bin Zhang, Jing Wang, Cui Wei, Xiuzhen Mao, Bin Yu

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引用次数: 0

Abstract

Objective: To assess the detection rate of exome sequencing (ES) in fetuses diagnosed as skeletal abnormalities (SKA) with normal karyotype or chromosomal microarray analysis (CMA) results.

Methods: We conducted electronic searches in four databases, focusing on studies involving ES in fetuses with SKA. Additional detection rate of ES compared to karyotype/CMA was calculated, followed by a meta-analysis. Subgroup analyses explored the influence of fetal phenotype on diagnostic outcomes.

Results: From 2,393 studies, 21 reports covering 476 fetuses were analyzed. Key findings include: (1) an additional detection rate of ES of 63.2% (Risk Difference (RD), 0.68 [95% CI, 0.60-0.76], p < 0.00001); (2) identification of 76 genes across 304 types of variants, with FGFR3, COL1A1, COL1A2, and COL2A1 being prevalent; (3) lower detection rates in fetuses with isolated short long bones compared to non-isolated conditions, though not significantly different (p = 0.35); (4) higher detection rates in subgroups with abnormal ossification, small chest, suspected long bone fractures or angulations, and skull abnormalities.

Conclusion: The meta-analysis indicates that genetic variation significantly contributes to fetal SKA, primarily due to single-gene variants. Consequently, ES should be used in the prenatal diagnosis of SKA fetuses in clinical practice.

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外显子组测序和产前骨骼异常：综合回顾、荟萃分析和前进方向。

目的：评价外显子组测序（ES）在核型正常或染色体微阵列分析（CMA）结果为骨骼异常（SKA）的胎儿中的检出率。方法：我们在四个数据库中进行电子检索，重点研究SKA胎儿的ES。计算ES与核型/CMA的附加检出率，并进行meta分析。亚组分析探讨胎儿表型对诊断结果的影响。结果：从2393项研究中，分析了21份报告，涵盖476例胎儿。主要发现包括：(1)ES的额外检出率为63.2%（风险差（Risk Difference， RD）， 0.68 [95% CI, 0.60-0.76], p < 0.00001）；(2)鉴定了304种变异类型中的76个基因，其中FGFR3、COL1A1、COL1A2和COL2A1是普遍存在的；(3)短长骨分离的胎儿检出率低于未分离的胎儿，但差异无统计学意义（p = 0.35）；(4)异常骨化、胸小、疑似长骨骨折或成角、颅骨异常亚组检出率较高。结论：荟萃分析表明，遗传变异对胎儿SKA有显著影响，主要是由于单基因变异。因此，在临床实践中，超声心动图应用于SKA胎儿的产前诊断。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.