Abstract
The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.
Highlights
Hydrops fetalis is a condition of excessively pathological fluid accumulation in more than two fetal tissues and body cavities
Trio-exome sequencing (ES) could deliver a diagnostic yield of 36% (10/28) in recurrent non-immune hydrops fetalis (NIHF) fetuses with no aneuploidy and causative copy number variations (CNV) detected and negative screening for alpha-thalassemia and betathalassemia
One reason was that recurrent fetal hydrops in the study represented a highly selected study group, which indicated that a higher incidence of single-gene disorders and non-genetic reasons contributing to NIHF has been ruled out as much as possible in the study following systematic work-up for NIHF
Summary
Hydrops fetalis is a condition of excessively pathological fluid accumulation in more than two fetal tissues and body cavities. It affects 1 in 1,700–3,000 pregnancies and is a life-threatening fetal situation. NIHF accounts for around 90% of cases of hydrops fetalis (Society for Maternal-Fetal Medicine, Norton et al, 2015). The etiologies of NIHF include genetic disorders, structural abnormalities, hematologic diseases, Exome Sequencing in Recurrent NIHF and Its Value on Management infections, twin-twin transfusion syndrome, extrathoracic tumors, and other causes. Genetic disorders, including chromosomal abnormalities, copy number variations (CNV), and single-gene disorders, have been reported to account for one-third of NIHF cases (Moreno et al, 2013; Society for Maternal-Fetal Medicine, Norton et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
