Expanded genetic testing of a pregnant woman with a congenital heart defect in her fetus
Pak V.S., Tetruashvili N.K., Bokerija E.L., Shubina Je., Zaretskaya N.V., Bolshakova A.S., Maslennikov D.N., Kochetkova T.O., Lyushnina D.G., Trofimov D.Yu.
Relevance: The prevalence of fetal heart defects varies by latitude, ranging from 4 to 50 cases per 1,000 live births. Annually, approximately 283.1 thousand children are born in the Russian Federation with congenital developmental anomalies, and approximately 30% of this population is affected by congenital heart defects (Rosstat data for 2023). In the context of antenatal fetal mortality in the Russian Federation, congenital developmental anomalies rank second, with fetal heart defects being the most common, accounting for 1.2% of stillbirths, and 16.7% of all fetal developmental anomalies.
At the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, an algorithm for the antenatal examination of pregnant women with fetal heart defects has been developed. This algorithm includes invasive prenatal diagnostics, expanded genetic testing, and genetic counseling for couples.
Objective: To describe the results of examinations of pregnant women with fetal heart defects according to an algorithm developed and implemented by V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Materials and methods: A pregnant woman with a fetal heart defect (coarctation of the aorta and atrial septal defect) underwent invasive antenatal diagnostics and expanded genetic testing. In the first stage, molecular karyotyping was performed using chromosomal microarray analysis of amniotic fluid, followed by sequencing of fetal and parental exomes.
Results: Extensive genetic analysis identified a potentially pathogenic variant within the NR2F2 gene in a fetus with a heart defect. This gene variant is associated with a spectrum of cardiac developmental defects, placental pathology, fetal growth restriction, and sexual developmental disorders. Subsequent Sanger family analysis confirmed that the identified NR2F2 gene variant in the fetus was de novo and not inherited from the parents, indicating a low risk of recurrence in future offspring.
Conclusion: Advanced ultrasound and genetic diagnostic modalities enable the accurate determination of the type of defect, genetic etiology (chromosomal or monogenic), and inheritance pattern during the antenatal period. Additionally, expanded prenatal counseling provides families with comprehensive information about the potential risks, complications, prognosis for disability, and survival of children with heart defects.
Authors’ contributions: Pak V.S., Tetruashvili N.K., Bokerija E.L., Trofimov D.Yu. – conception and design of the study; Pak V.S., Zaretskaya N.V., Bolshakova A.S., Lyushnina D.G., Maslennikov D.N., Kochetkova T.O. – data collection and processing; Pak V.S., Tetruashvili N.K. – drafting of the manuscript; Tetruashvili N.K., Bokerija E.L., Shubina Je., Bolshakova A.S., Trofimov D.Yu. – editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The state order under the topic: "Development of a test system for prenatal diagnostics of fetal cardiopathology".
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication: The couple signed a voluntary informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Pak V.S., Tetruashvili N.K., Bokerija E.L., Shubina Je., Zaretskaya N.V., Bolshakova A.S., Maslennikov D.N., Kochetkova T.O., Lyushnina D.G., Trofimov D.Yu.
Expanded genetic testing of a pregnant woman with a congenital heart defect in her fetus.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (11): 83-89 (in Russian)
https://dx.doi.org/10.18565/aig.2024.189
Keywords
congenital heart defect
NR2F2 gene
chromosomal microarray analysis
exome sequencing of congenital heart defect of the fetus
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Received 01.08.2024
Accepted 10.10.2024
About the Authors
Viktoriia S. Pak, PhD student, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(913)897-28-49,v_pak@oparina4.ru, https://orcid.org/0009-0002-1444-9071
Nana K. Tetruashvili, PhD, Head of the Obstetric Department of Pregnancy Pathology No. 2, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
4 Acad. Oparin str., Moscow, Russia, +7(495)438-14-77, n_tetruashvili@oparina4.ru, https://orcid.org/0000-0002-9201-2281
Ekaterina L. Bokerija, PhD, Researcher at the Department of Pathology for Newborn and Prematurely-Born Children No. 2, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-27-05, e_bokeriya@oparina4.ru, https://orcid.org/0000-0002-8898-9612
Jekaterina Shubina, PhD in Biology, Head of the Laboratory of Genomic Data Analysis, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)531-44-44, e_shubina@oparina4.ru, https://orcid.org/0000-0003-4383-7428
Nadezhda V. Zaretskaya, PhD, Head of the Laboratory of Clinical Genetics of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-24-11, n_zaretskaya@oparina4.ru, https://orcid.org/0000-0001-6754-3833
Anna S. Bolshakova, MD, Geneticist, Department of Clinical Genetics of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-24-11, a_bolshakova@oparina4.ru, https://orcid.org/0000-0002-7508-0899
Daria G. Lyushnina, PhD student, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(906)308-60-78,
d_lyushnina@oparina4.ru, https://orcid.org/0009-0004-3160-8737
Dmitry N. Maslennikov, MD, Geneticist at the Laboratory of Genomic Data Analysis of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, d_maslennikov@oparina4.ru, https://orcid.org/0000-0001-5916-0672
Taisiya O. Kochetkova, Biologist at the Laboratory of Molecular and Genetic Methods of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, t_kochetkova@oparina4.ru, https://orcid.org/0000-0003-0215-3636
Dmitry Yu. Trofimov, Dr. Bio. Sci, Professor of the RAS, Corresponding Member of the RAS, Director of the Institute of Reproductive Genetics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 4 Acad. Oparin str., Moscow, Russia, 117997, +7(495)438-49-51, d_trofimov @oparina4.ru, https://orcid.org/0000-0002-1569-8486
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