The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215000, Jiangsu, China.
Orphanet J Rare Dis. 2024 Sep 9;19(1):330. doi: 10.1186/s13023-024-03340-5.
Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies.
As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed.
The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance.
Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.
全外显子测序（WES）已被推荐用于研究胎儿结构异常的遗传原因。在这项回顾性研究中，我们旨在评估 WES 在我们因结构异常而流产或终止妊娠的家庭队列中的诊断产量。
由于基于外显子的 CNV 分析可以检测到非整倍体、三倍体和拷贝数变异（CNVs），因此在本研究中仅进行 WES。并分析了 375 例经 WES 评估的病例的结果。
总体检测率为 32.3%（121/375），包括非整倍体和三倍体（7.5%，28/375）、CNVs（5.1%，19/375）和单核苷酸变异（SNVs）/插入或缺失（Indels）（19.7%，74/375）。其中，可能致病（LP）或致病（P）CNVs 的诊断率为 4.8%（18/375），LP 或 P SNVs/Indels 的诊断率为 15.2%（57/375）。另外 4.8%（18/375）的病例的 CNVs 或 SNVs/Indels 被归类为具有潜在临床意义的不确定意义（VUS）变异。
我们的研究结果扩展了与胎儿异常相关的遗传变异的已知突变谱，增加了我们对产前表型的理解，并能够更准确地为未来妊娠的复发风险提供咨询。
