对超声异常的死胎进行全外显子组测序：一项回顾性分析。

Whole-exome sequencing in deceased fetuses with ultrasound anomalies: a retrospective analysis.

机构信息

Department of Obstetrics and Gynecology, Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

BMC Med Genomics. 2023 Feb 16;16(1):25. doi: 10.1186/s12920-022-01427-1.

DOI:10.1186/s12920-022-01427-1

PMID:36797717

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9936674/

Abstract

BACKGROUND

Whole-exome sequencing (WES) is an effective method in the prenatal setting for identification of the underlying genetic etiology of fetal ultrasound abnormalities. To investigate the diagnostic value of WES in fetuses with ultrasound abnormalities that resulted in fetal demise or pregnancy termination.

METHODS

61 deceased fetuses with ultrasound abnormalities and normal copy number variation Sequencing were retrospectively collected. Proband-only or trio-WES were performed on the products of conception.

RESULT

Collectively, 28 cases were positive with 39 variants (10 pathogenic, 22 likely pathogenic and 7 variants of uncertain significance) of 18 genes, and the overall diagnostic rate was 45.9% (28/61), of which 39.2% (11/28) were de novo variants. In addition, 21 variants in 11 genes among the positive cases had not been previously reported. The diagnostic yield for definitive findings for trio analysis was 55.9% (19/34) compared to 33.3% (9/27) for singletons. The most common ultrasound abnormalities were skeletal system abnormalities 39.2% (11/28), followed by multiple system abnormalities (17.9%, 5/28) and genitourinary abnormalities (17.9%, 5/28).

CONCLUSION

Our results support the use of WES to identify genetic etiologies of ultrasound abnormalities and improve understanding of pathogenic variants. The identification of disease-related variants provided information for subsequent genetic counseling of recurrence risk and management of subsequent pregnancies.

摘要

背景

全外显子组测序（WES）是产前检测胎儿超声异常潜在遗传病因的有效方法。本研究旨在探讨 WES 对导致胎儿死亡或妊娠终止的超声异常胎儿的诊断价值。

方法

回顾性收集 61 例超声异常且拷贝数正常的死亡胎儿。对胎儿组织进行单样本或三亲子代 WES 检测。

结果

共发现 28 例阳性，携带 18 个基因中的 39 种变异（10 种致病性、22 种可能致病性和 7 种意义不明的变异），总体诊断率为 45.9%（28/61），其中 39.2%（11/28）为新生变异。此外，阳性病例中的 21 种变异在 11 个基因中尚未见报道。三亲子代分析的明确检测结果率为 55.9%（19/34），而单样本分析的结果率为 33.3%（9/27）。最常见的超声异常为骨骼系统异常 39.2%（11/28），其次为多系统异常（17.9%，5/28）和生殖泌尿系统异常（17.9%，5/28）。