Open AccessNext-Generation Sequencing Gene Panels and “Solo” Clinical Exome Sequencing Applied in Structurally Abnormal Fetuses
Author(s) -
Montse Pauta,
Bieito Campos,
Maria Segura-Puimedon,
Gemma Arca,
Alfons Nadal,
A. Tubau,
Silvia Pérez,
E. Marimón,
Lourdes Martín,
E. López-Quesada,
J. Sabrià,
Begoña Muñoz,
Esperanza Garcı́a,
F. Paz y Miño,
V. Borobio,
O. Gómez,
E. Eixarch,
Mónica Luján López,
Montserrat Rovira,
Antoni Borrell
Publication year - 2021
Publication title -
fetal diagnosis and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.976
H-Index - 60
eISSN - 1421-9964
pISSN - 1015-3837
DOI - 10.1159/000519701
Subject(s) - exome sequencing , fetus , dna sequencing , medicine , gene , genetics , mendelian inheritance , mutation , pathology , bioinformatics , biology , pregnancy
Objective: 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. Methodology: 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. Results: 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. Conclusions: A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.