Song Weian,Gu Shuo.Research advances on applying whole exome sequencing for genetic diagnosis of fetal ventriculomegaly[J].Journal of Clinical Pediatric Surgery,2026,(04):396-400.[doi:10.3760/cma.j.cn101785-20260205-00052]
全外显子组测序在胎儿侧脑室增宽遗传诊断中的应用进展
- Title:
- Research advances on applying whole exome sequencing for genetic diagnosis of fetal ventriculomegaly
- Keywords:
- Fetal Ventriculomegaly; Whole Exome Sequencing; Prenatal Diagnosis; Genetic Diagnosis; Genetic Susceptibility to Disease
- 摘要:
- 胎儿侧脑室增宽(fetal ventriculomegaly,FVM)是产前超声检出率较高的中枢神经系统异常之一。其病因复杂,遗传因素起重要作用。传统产前遗传学诊断技术,如染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA)对于孤立性FVM的病因检出率相对有限。高通量测序技术中的全外显子组测序(whole exome sequencing,WES)可有效检测与胎儿中枢神经发育障碍相关的单基因致病位点,提升FVM遗传病因的诊断效能。研究显示,在CMA检测结果阴性的非孤立性FVM病例中,WES诊断率达10%~30%;在孤立性FVM中,WES亦可获得8%~10%的额外诊断率,并发现 L1CAM、AP1S2、MPDZ、CCDC88C等基因发生的致病性变异。WES的应用为胎儿预后评估、家庭再发风险咨询以及产前治疗干预提供了重要遗传学依据,正逐渐成为产前遗传诊断领域的重要工具。然而,WES仍面临变异位点解读困难、偶然发现的处理以及伦理问题等诸多挑战。本文综述WES在FVM产前遗传诊断中的应用价值及对临床决策的影响、FVM的常见致病基因以及当前面临的挑战与未来展望。
- Abstract:
- Fetal ventriculomegaly (FVM) is one of central nervous system (CNS) abnormalities with a high detection rate on prenatal ultrasound.Its etiology has remained rather complex and genetic factors play some crucial roles.Traditional prenatal genetic diagnostic techniques of chromosomal karyotyping and chromosomal microarray analysis (CMA) have relatively hindered diagnostic yields for identifying the etiology of isolated FVM.Whole exome sequencing (WES),a high-throughput sequencing technology,can effectively detect single-gene pathogenic variants associated with fetal CNS developmental disorders,significantly improving the diagnostic efficiency for genetic etiology of FVM.This systematical review focused upon the application value of WES in prenatal genetic diagnosis of FVM,common pathogenic genes,impact on clinical decision-making,current challenges and future prospects.Recent studies have demonstrated that in non-isolated FVM cases with negative CMA results,the diagnostic yield of WES reached 10%-30%; in isolated FVM,WES could also provide an additional diagnostic yield of 8%-10%,identifying pathogenic variants in such genes as L1CAM,AP1S2,MPDZ and CCDC88C.The application of WES provides an important genetic basis for precise fetal prognosis assessment,family recurrence risk counseling and prenatal therapeutic interventions.It is gradually becoming a key tool in the field of prenatal genetic diagnosis.However,WES still has inherent challenges of difficulties in variant interpretation,management of incidental findings and ethical issues.In the future,with the accumulation of population data and the development of bioinformatics technologies,WES shall play an even more important role in the precision medicine management of fetal FVM.
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备注/Memo
收稿日期:2026-2-5。
基金项目:海南省重点研发项目(ZDYF2022SHFZ292)
通讯作者:顾硕,Email:gushuo007@163.com