{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:26Z","timestamp":1791521426880,"version":"4.3.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20250604145756074"],"award-info":[{"award-number":["JCYJ20250604145756074"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Deletions and duplications within the 15q11q13 chromosomal region are associated with Prader-Willi syndrome, Angelman syndrome, and 15q11q13 duplication syndrome. However, prenatal ultrasound findings were unremarkable in the majority of affected fetuses. The aim of this study was to evaluate the efficacy of non-invasive prenatal screening (NIPS) in identifying these syndromes in 90,693 pregnancies within the general population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 90,693 pregnant women who underwent NIPS at Longgang Maternal and Child Health Hospital in Shenzhen from November 2022 to January 2026. For high-risk 15q11q13 copy number variations (CNVs) identified, we performed chromosomal microarray analysis (CMA) on amniotic fluid, followed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) or further CMA to determine the CNVs\u2019 genetic origin, with subsequent follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NIPS screening identified 4 high-risk cases for 15q11q13 deletion and 7 for duplication. Among the deletion cases, 3 were confirmed by CMA to have a 5\u20136\u00a0Mb deletion (2 maternal, 1 unverified), while 1 declined further testing. For duplication, 6 underwent amniocentesis, with CMA confirming 5 cases (2 maternal, 2 paternal, 1 unverified), 1 normal result, and 1 declined further testing. Of the 8 true-positive cases, 7 had normal ultrasounds, but 1 fetus with duplication exhibited growth retardation. Pregnancy outcomes included 6 terminations, one delivery with paternal duplication showing mild language delay at nearly 2 years, and another with maternal duplication lost to follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NIPS can effectively detect CNVs at the 15q11q13 locus with a high positive predictive value, but its sensitivity, specificity, negative predictive value, and false-negative rate could not be determined in this study due to the lack of confirmatory testing in low-risk cases. Invasive prenatal diagnosis remains essential for validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1937108","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:02Z","timestamp":1791519962000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance of non-invasive prenatal screening for 15q11q13 copy number variations in a cohort of 90,693 pregnancies"],"prefix":"10.3389","volume":"17","author":[{"given":"Diyu","family":"Chen","sequence":"first","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Niu","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenming","family":"Li","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Cong","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingnan","family":"Sun","sequence":"additional","affiliation":[{"name":"Stem Cell Research Center, Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Central Laboratory (Genetics Lab), Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Affiliated Shenzhen Women and Children\u2019s Hospital (Longgang) of Shantou University Medical College)","place":["Shenzhen, China"]},{"name":"Longgang District Key Laboratory for Birth Defects Prevention","place":["Shenzhen, China"]},{"name":"GuangDong Engineering Technology Research Center of Genomics and Precision Imaging","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.ejogrb.2021.01.008","article-title":"Non invasive prenatal testing (NIPT) for common aneuploidies and beyond","volume":"258","author":"Alberry","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/genes12040501","article-title":"Chances and challenges of New Genetic Screening Technologies (NIPT) in prenatal medicine from a clinical perspective: a narrative review","volume":"12","author":"Bedei","year":"2021","journal-title":"Genes (Basel)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.3390\/genes15101304","article-title":"Chromosome 15q11-q13 duplication syndrome: a review of the literature and 14 new cases","volume":"15","author":"Bisba","year":"2024","journal-title":"Genes (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.3390\/ijms27031270","article-title":"Clinical presentation, genetics, and laboratory testing with integrated genetic analysis of molecular mechanisms in prader-willi and angelman syndromes: a review","volume":"27","author":"Butler","year":"2026","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1016\/j.ajhg.2024.07.002","article-title":"Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain","volume":"111","author":"Dias","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ajog.2016.04.029","article-title":"Noninvasive prenatal screening or advanced diagnostic testing: caveat emptor","volume":"215","author":"Evans","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1002\/pd.5049","article-title":"Discordant non-invasive prenatal testing (NIPT) - a systematic review","volume":"37","author":"Hartwig","year":"2017","journal-title":"Prenat. Diagn"},{"key":"B7","doi-asserted-by":"publisher","first-page":"102899","DOI":"10.1016\/j.conb.2024.102899","article-title":"Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome","volume":"88","author":"Krzeski","year":"2024","journal-title":"Curr. Opin. Neurobiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/uog.14911","article-title":"Detection of fetal copy number variants by non-invasive prenatal testing for common aneuploidies","volume":"47","author":"Li","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1007\/s00404-022-06908-3","article-title":"Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China","volume":"308","author":"Liu","year":"2023","journal-title":"Arch. Gynecol. Obstet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.3390\/ijms24032150","article-title":"Clinical trials in Prader-Willi Syndrome: a review","volume":"24","author":"Mahmoud","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1002\/ajmg.a.35907","article-title":"Clinical and genetic study of a family with a paternally inherited 15q11-q13 duplication","author":"Marini","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41431-023-01336-6","article-title":"Population screening for 15q11-q13 duplications: corroboration of the difference in impact between maternally and paternally inherited alleles","volume":"32","author":"Parijs","year":"2024","journal-title":"Eur. J. Hum. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"12830","DOI":"10.1038\/s41598-025-97973-6","article-title":"Prenatal diagnosis of imprinted associated chromosome abnormalities identified by noninvasive prenatal testing (NIPT)","volume":"15","author":"Peng","year":"2025","journal-title":"Sci. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.neuroscience.2020.02.017","article-title":"Angelman syndrome: from mouse models to therapy","volume":"445","author":"Rotaru","year":"2020","journal-title":"Neuroscience"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1146669","DOI":"10.3389\/fgene.2023.1146669","article-title":"Positive cfDNA screening results for 22q11.2 deletion syndrome-clinical and laboratory considerations","volume":"14","author":"Soster","year":"2023","journal-title":"Front. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"103001","DOI":"10.1016\/j.conb.2025.103001","article-title":"Neurodevelopmental impact of CNV models in ASD: recent advances and future directions","volume":"92","author":"Tamada","year":"2025","journal-title":"Curr. Opin. Neurobiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1002\/aur.1284","article-title":"The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature","volume":"6","author":"Urraca","year":"2013","journal-title":"Autism Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1089\/cap.2021.0046","article-title":"Maternal duplication 15q11-13 syndrome with autism spectrum disorder: mood stabilization by carbamazepine","volume":"32","author":"Viamontes","year":"2022","journal-title":"J. Child. Adolesc. Psychopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13039-023-00656-y","article-title":"Application of non-invasive prenatal testing to 91,280 spontaneous pregnancies and 3477 pregnancies conceived by in vitro fertilization","volume":"16","author":"Wei","year":"2023","journal-title":"Mol. Cytogenet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/pd.6312","article-title":"Non-invasive prenatal testing for the detection of trisomies 21, 18, and 13 in pregnant women with various clinical indications: a multicenter observational study of 1,854,148 women in China","volume":"43","author":"Xiang","year":"2023","journal-title":"Prenat. Diagn"},{"key":"B22","doi-asserted-by":"publisher","first-page":"24755","DOI":"10.1038\/s41598-025-10446-8","article-title":"Determining the origin of genome aberrations improves the positive predictive value of NIPT for 22q11.2 deletion syndrome","volume":"15","author":"Xiang","year":"2025","journal-title":"Sci. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.3390\/ijms26052304","article-title":"Unraveling the roles of UBE3A in neurodevelopment and neurodegeneration","volume":"26","author":"Yang","year":"2025","journal-title":"Int. J. Mol. Sci."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1937108\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:03Z","timestamp":1791519963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1937108\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":23,"alternative-id":["10.3389\/fgene.2026.1937108"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1937108","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"article-number":"1937108"}}