Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), BCNatal, Barcelona, Spain,
qGenomics. Esplugues de Llobregat, Catalonia, Spain.
Fetal Diagn Ther. 2021;48(10):746-756. doi: 10.1159/000519701. Epub 2021 Nov 12.
The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and "solo" clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation.
Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies.
During the study period (2015-2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES.
A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.
本研究旨在评估两种不同的下一代测序（NGS）方法的诊断收益：基因panel 和“独奏”临床外显子组测序（solo-CES），应用于结构异常且染色体微阵列分析（CMA）正常的胎儿，且不存在已知家族突变。
基因panel 涵盖了 2 到 140 个基因，主要应用于持续性颈后褶皱/胎儿水肿和大的高回声肾脏。独奏-CES 仅对胎儿进行测序，仅解释在线孟德尔遗传数据库（OMIM）基因，应用于多系统或复发性结构异常。
在研究期间（2015-2020 年），对 148 例结构异常且 CMA 正常的胎儿进行了 153 次 NGS 研究。总体诊断收益占样本的 35%（53/153）和胎儿的 36%（53/148）。基因panel 的诊断收益为 31%（15/49），与 solo-CES 的 37%（38/104）相似。
通过基因panel 和 solo-CES，在选择的胎儿结构异常中，有 35%的病例确定了单基因疾病是其根本原因。
