{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:40:35Z","timestamp":1764700835849,"version":"3.46.0"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Prenatal genetic testing plays a crucial role in prenatal diagnosis and is traditionally performed when abnormalities are detected on fetal ultrasound. With the widespread availability of next-generation sequencing (NGS), genetic screening is increasingly being applied to fetuses with normal ultrasound findings. This study aimed to evaluate the diagnostic yield and outcomes of NGS panel testing in a large cohort of pregnant women with sonographically normal fetuses. A retrospective analysis was conducted on 1,820 sonographically normal fetuses that underwent fetal\u00a0NGS-targeted\u00a0panel testing based on parental requests between June 2021 and June 2023. Among the 1,820 cases analyzed, no pathogenic mutations were identified in 833 (45.8%), 893 (49.1%) had an abnormal carrier status, and 94 (5.2%) exhibited pathogenic conditions, including 25 autosomal dominant, 29 autosomal recessive, 39 X-linked (35 hemizygous glucose-6-phosphate dehydrogenase [\n                    <jats:italic>G6PD<\/jats:italic>\n                    ] cases), and one mitochondrial disorder. The most common autosomal recessive mutation was a homozygous pathogenic variant of\n                    <jats:italic>GJB2<\/jats:italic>\n                    (19 cases). Furthermore, 48 patients carried heterozygous\n                    <jats:italic>G6PD<\/jats:italic>\n                    mutations, and 344 patients were identified as carriers of\n                    <jats:italic>GJB2<\/jats:italic>\n                    variants. Other notable findings included 15 cases of familial hypercholesterolemia, five cases of Noonan syndrome, and two cases of osteogenesis imperfecta. The rare disorders identified were Wilson\u2019s disease, cystic fibrosis, Cockayne syndrome, and ototoxic hearing loss, all of which were observed in a single case. A fetal NGS-targeted panel yielded critical findings in 5.16% of sonographically normal fetuses, emphasizing its potential use in prenatal diagnosis. Effective screening requires careful variant selection and detailed pre- and post-test genetic counseling to ensure the clinical relevance and informed decision-making of parents.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0336979","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T18:29:02Z","timestamp":1764700142000},"page":"e0336979","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted fetal NGS panel reveals genetic conditions in sonographically normal fetuses: Insights from a large cohort study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-9210","authenticated-orcid":true,"given":"Han-Ying","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Yun","family":"Tai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ti-Jia","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0753-2793","authenticated-orcid":true,"given":"Shin-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi-Ming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Nan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsang-Ming","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"issue":"23","key":"pone.0336979.ref001","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa1201569","article-title":"Karyotype versus microarray testing for genetic abnormalities after stillbirth","volume":"367","author":"UM Reddy","year":"2012","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0336979.ref002","article-title":"The use of chromosomal microarray for prenatal diagnosis","volume":"215","author":"Society for Maternal-Fetal Medicine, Electronic address PSO","year":"2016","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"pone.0336979.ref003","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/pd.6157","article-title":"International Society for Prenatal Diagnosis Updated Position Statement on the use of genome-wide sequencing for prenatal diagnosis","volume":"42","author":"ISPD Board of Directors","year":"2022","journal-title":"Prenat Diagn"},{"issue":"1","key":"pone.0336979.ref004","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":"S Best","year":"2018","journal-title":"Prenat Diagn"},{"issue":"5","key":"pone.0336979.ref005","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s41436-020-01067-9","article-title":"Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes","volume":"23","author":"LK Tolusso","year":"2021","journal-title":"Genet Med"},{"issue":"1","key":"pone.0336979.ref006","doi-asserted-by":"crossref","first-page":"101008","DOI":"10.1016\/j.gim.2023.101008","article-title":"Ready or not, genomic screening of fetuses is already here","volume":"26","author":"NB Gold","year":"2024","journal-title":"Genet Med"},{"issue":"16","key":"pone.0336979.ref007","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical whole-exome sequencing for the diagnosis of mendelian disorders","volume":"369","author":"Y Yang","year":"2013","journal-title":"N Engl J 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