{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:00:13Z","timestamp":1773666013078,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center of Postgraduate Medical Education","award":["Minigrant-501-1-106-44-20\/MG4"],"award-info":[{"award-number":["Minigrant-501-1-106-44-20\/MG4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. Methods: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. Results: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. Conclusions: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.<\/jats:p>","DOI":"10.3390\/genes13050724","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-6425","authenticated-orcid":false,"given":"Anna","family":"Kuci\u0144ska-Chahwan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"},{"name":"Department of Obstetrics and Gynecology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-8751","authenticated-orcid":false,"given":"Maciej","family":"Geremek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Roszkowski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bijok","sequence":"additional","affiliation":[{"name":"Department of Gynecology Oncology and Obstetrics, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Massalska","sequence":"additional","affiliation":[{"name":"Department of Gynecology Oncology and Obstetrics, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5780-5983","authenticated-orcid":false,"given":"Micha\u0142","family":"Ciebiera","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hildeberto","family":"Correia","sequence":"additional","affiliation":[{"name":"Cytogenetics Unit, Department of Human Genetics, Nacional Health Institute Doutor Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Pereira-Caetano","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Barreta","sequence":"additional","affiliation":[{"name":"Medical Genetics Service, Joaquim Chaves Sa\u00fade, 1495-148 Oeiras, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5295-7363","authenticated-orcid":false,"given":"Anna","family":"Kutkowska-Ka\u017amierczak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"W\u0142asienko","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-210X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Krajewska-Walasek","sequence":"additional","affiliation":[{"name":"Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"W\u0119grzyn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Perinatology and Gynaecology, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lech","family":"Dudarewicz","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldemar","family":"Krzeszowski","sequence":"additional","affiliation":[{"name":"Department of Perinatology and Gynecology, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"},{"name":"Salve Medica, 91-211 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-8078","authenticated-orcid":false,"given":"Magda","family":"Rybak-Krzyszkowska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Perinatology, University Hospital in Krakow, 31-501 Warsaw, Poland"},{"name":"Hi-Gen Medical Centre, 30-552 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2008). Update on Overall Prevalence of Major Birth Defects\u2013Atlanta, Georgia, 1978\u20132005. MMWR Morb. Mortal. Wkly. Rep., 57, 1\u20135."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/tera.1420390404","article-title":"Congenital defect rates among spontaneous abortuses: Twenty years of monitoring","volume":"39","author":"Shepard","year":"1989","journal-title":"Teratology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Society for Maternal-Fetal Medicine (2016). Committee Opinion No. 682 Summary: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. Obstet. Gynecol., 128, 1462\u20131463.","DOI":"10.1097\/AOG.0000000000001814"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1056\/NEJMoa1203382","article-title":"Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis","volume":"367","author":"Wapner","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s10815-020-01812-8","article-title":"In-house genetic counseling increases the detection of abnormal karyotypes\u2014A 26-year experience in prenatal diagnosis in a single tertiary referral hospital in Poland","volume":"37","author":"Bijok","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"International Society for Prenatal Diagnosis, Society for Maternal and Fetal Medicine, Perinatal Quality Foundation (2018). Joint Position Statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat. Diagn., 38, 6\u20139.","DOI":"10.1002\/pd.5195"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ajhg.2009.09.003","article-title":"Clinical diagnostics in human genetics with semantic similarity searches in ontologies","volume":"85","author":"Schulz","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","first-page":"D1207","article-title":"The Human Phenotype Ontology in 2021","volume":"49","author":"Gargano","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1101\/gr.160325.113","article-title":"Improved exome prioritization of disease genes through cross-species phenotype comparison","volume":"24","author":"Robinson","year":"2013","journal-title":"Genome Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"490","DOI":"10.5603\/GP.2020.0110","article-title":"Practice guidelines of the Polish Society of Gynecologists and Obstetricians\u2014Ultrasound Section for ultrasound screening in uncomplicated pregnancy\u20142020","volume":"91","author":"Borowski","year":"2020","journal-title":"Ginekol. Polska"},{"key":"ref_12","unstructured":"(2022, April 18). Republic of Poland, Journal of Laws No. 210, Item 2135, Dated 27 August 2004, Available online: https:\/\/isap.sejm.gov.pl\/isap.nsf\/DocDetails.xsp?id=wdu20042102135."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/gim.2016.190","article-title":"Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): A policy statement of the American College of Medical Genetics and Genomics","volume":"19","author":"Kalia","year":"2017","journal-title":"Genet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/pd.5102","article-title":"Promises, pitfalls and practicalities of prenatal whole exome sequencing","volume":"38","author":"Best","year":"2018","journal-title":"Prenat. Diagn."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mellis, R., Oprych, K., Scotchman, E., Hill, M., and Chitty, L.S. (2022). Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta-analysis. Prenat. Diagn.","DOI":"10.1002\/pd.6115"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0140-6736(18)31940-8","article-title":"Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): A cohort study","volume":"393","author":"Lord","year":"2019","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S0140-6736(18)32042-7","article-title":"Whole-exome sequencing in the evaluation of fetal structural anomalies: A prospective cohort study","volume":"393","author":"Petrovski","year":"2019","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/uog.18915","article-title":"Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities","volume":"51","author":"Fu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"627204","DOI":"10.3389\/fgene.2021.627204","article-title":"The Added Value of Whole-Exome Sequencing for Anomalous Fetuses with Detailed Prenatal Ultrasound and Postnatal Phenotype","volume":"12","author":"He","year":"2021","journal-title":"Front. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/cge.13976","article-title":"Molecular diagnosis for 55 fetuses with skeletal dysplasias by whole-exome sequencing: A retrospective cohort study","volume":"100","author":"Zhang","year":"2021","journal-title":"Clin. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"728544","DOI":"10.3389\/fgene.2021.728544","article-title":"Whole Exome Sequencing Analysis in Fetal Skeletal Dysplasia Detected by Ultrasonography: An Analysis of 38 Cases","volume":"12","author":"Peng","year":"2021","journal-title":"Front. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/uog.22072","article-title":"COngenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: Prospective cohort study and systematic review","volume":"57","author":"Mone","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.gim.2021.09.016","article-title":"Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts","volume":"24","author":"Marangoni","year":"2022","journal-title":"Genet Med."},{"key":"ref_24","first-page":"104410","article-title":"Challenges in variant interpretation in prenatal exome sequencing","volume":"65","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1136\/jmedgenet-2020-106867","article-title":"Genotype-first in a cohort of 95 fetuses with multiple congenital abnormalities: When exome sequencing reveals unexpected fetal pheno-type-genotype correlations","volume":"58","author":"Lefebvre","year":"2021","journal-title":"J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13073-018-0582-x","article-title":"Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder","volume":"10","author":"Normand","year":"2018","journal-title":"Genome Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1093\/hmg\/ddw054","article-title":"Recessive NEK9 mutation causes a lethal skeletal dysplasia with evidence of cell cycle and ciliary defects","volume":"25","author":"Casey","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mone, F., Abu Subieh, H., Doyle, S., Hamilton, S., McMullan, D.J., Allen, S., Marton, T., Williams, D., and Kilby, M.D. (2021). Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: Cohort study. Ultrasound Obstet. Gynecol.","DOI":"10.1002\/uog.24842"},{"key":"ref_29","first-page":"8","article-title":"Parental motivations for and adaptation to trio-exome sequencing in a prospective prenatal testing cohort: Beyond the diagnosis","volume":"1","author":"Talati","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Talati, A.N., Gilmore, K.L., Hardisty, E., and Vora, N.L. (2022). How can prenatal exome sequencing inform future pregnancies?. Am. J. Obstet. Gynecol.","DOI":"10.1016\/j.ajog.2022.02.008"},{"key":"ref_31","first-page":"7","article-title":"Trio exome sequencing is highly relevant in prenatal diagnostics","volume":"1","author":"Gabriel","year":"2021","journal-title":"Prenat. Diagn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/aogs.13871","article-title":"Implementation of exome sequencing in fetal diagnostics\u2014Data and experiences from a tertiary center in Denmark","volume":"99","author":"Becher","year":"2020","journal-title":"Acta Obstet. Gynecol. Scand."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:13Z","timestamp":1760137093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/5\/724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,21]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["genes13050724"],"URL":"https:\/\/doi.org\/10.3390\/genes13050724","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,21]]}}}