{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:24:17Z","timestamp":1787505857684,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC1005300"],"award-info":[{"award-number":["2021YFC1005300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021YFS0078 2022YFS0078"],"award-info":[{"award-number":["2021YFS0078 2022YFS0078"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:bold>Objectives:<\/jats:bold>\n                    The study aimed to investigate the clinical use of noninvasive prenatal testing (NIPT) for common fetal aneuploidies as a prenatal screening tool for the detection of rare chromosomal abnormalities (RCAs).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Gravidas with positive NIPT results for RCAs who subsequently underwent amniocentesis for a single nucleotide polymorphism array (SNP array) were recruited. The degrees of concordance between the NIPT and SNP array were classified into full concordance, partial concordance, and discordance. The positive predictive value (PPV) was used to evaluate the performance of NIPT.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The screen-positivity rate of NIPT for RCAs was 0.5% (842\/158,824). Of the 528 gravidas who underwent amniocentesis, 29.2% (154\/528) were confirmed to have positive prenatal SNP array results. PPVs for rare autosomal trisomies (RATs) and segmental imbalances were 6.1% (7\/115) and 21.1% (87\/413), respectively. Regions of homozygosity\/uniparental disomy (ROH\/UPD) were identified in 9.5% (50\/528) of gravidas. The PPV for clinically significant findings was 8.0% (42\/528), including 7 cases with mosaic RATs, 30 with pathogenic\/likely pathogenic copy number variants, and 5 with imprinting disorders.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    NIPT for common fetal aneuploidies yielded low PPVs for RATs, moderate PPVs for segmental imbalances, and incidental findings for ROH\/UPD. Due to the low PPV for clinically significant findings, NIPT for common fetal aneuploidies need to be noticed for RCAs.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.955694","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T07:45:35Z","timestamp":1664178335000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies"],"prefix":"10.3389","volume":"13","author":[{"given":"Ting","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Like","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1097\/01.AOG.0000438962.16108.d1","article-title":"Committee opinion no. 581: The use of chromosomal microarray analysis in prenatal diagnosis","volume":"122","year":"2013","journal-title":"Obstet. Gynecol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1097\/AOG.0000000000003070","article-title":"Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226","volume":"136","year":"2020","journal-title":"Obstet. Gynecol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1097\/AOG.0000000000001051","article-title":"Committee opinion No. 640: Cell-Free DNA screening for fetal aneuploidy","volume":"126","year":"2015","journal-title":"Obstet. Gynecol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1002\/uog.19014","article-title":"Genome-wide non-invasive prenatal screening for all cytogenetically visible imbalances","volume":"51","author":"Benn","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1373\/clinchem.2013.202663","article-title":"Integration of noninvasive DNA testing for aneuploidy into prenatal care: What has happened since the rubber met the road?","volume":"60","author":"Bianchi","year":"2014","journal-title":"Clin. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1086\/302661","article-title":"Long homozygous chromosomal segments in reference families from the centre d'Etude du polymorphisme humain","volume":"65","author":"Broman","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/hmg\/ddl473","article-title":"Effects of genome-wide heterozygosity on a range of biomedically relevant human quantitative traits","volume":"16","author":"Campbell","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40246-019-0250-2","article-title":"Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions\/microduplications in a cohort of 42, 910 single pregnancies with different clinical Features","volume":"13","author":"Chen","year":"2019","journal-title":"Hum. Genomics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/gim.2017.91","article-title":"Diagnostic cytogenetic testing following positive noninvasive prenatal screening results: A clinical laboratory practice resource of the American College of medical genetics and genomics (ACMG).","volume":"19","author":"Cherry","year":"2017","journal-title":"Genet. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/pd.5216","article-title":"Current controversies in prenatal diagnosis 2: Cell-free DNA prenatal screening should be used to identify all chromosome abnormalities","volume":"38","author":"Chitty","year":"2018","journal-title":"Prenat. Diagn."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/pd.1884","article-title":"Resolution of trisomic mosaicism in prenatal diagnosis: Estimated performance of a 50K SNP microarray","volume":"27","author":"Cross","year":"2007","journal-title":"Prenat. Diagn."},{"key":"B12","doi-asserted-by":"publisher","first-page":"527.e1","DOI":"10.1016\/j.ajog.2014.08.006","article-title":"Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing","volume":"211","author":"Dar","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1038\/s41436-020-0782-9","article-title":"Diagnostic testing for uniparental disomy: A points to consider statement from the American College of medical genetics and genomics (ACMG)","volume":"22","author":"Del Gaudio","year":"2020","journal-title":"Genet. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/ajmg.1320060207","article-title":"A new genetic concept: Uniparental disomy and its potential effect, isodisomy.","volume":"6","author":"Engel","year":"1980","journal-title":"Am. J. Med. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1517\/14712598.2012.670632","article-title":"Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.","volume":"12","author":"Faas","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.gim.2021.10.004","article-title":"Interpretation and reporting of large regions of homozygosity and suspected consanguinity\/uniparental disomy, 2021 revision: A technical standard of the American College of medical genetics and genomics (ACMG).","volume":"24","author":"Gonzales","year":"2022","journal-title":"Genet. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.bpobgyn.2017.02.004","article-title":"Chromosomal mosaicism in the fetoplacental unit.","volume":"42","author":"Grati","year":"2017","journal-title":"Best. Pract. Res. Clin. Obstet. Gynaecol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/gim.2014.3","article-title":"Fetoplacental mosaicism: Potential implications for false-positive and false-negative noninvasive prenatal screening results.","volume":"16","author":"Grati","year":"2014","journal-title":"Genet. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/gim.2016.97","article-title":"Noninvasive prenatal screening for fetal aneuploidy, 2016 update: A position statement of the American College of medical genetics and genomics","volume":"18","author":"Gregg","year":"2016","journal-title":"Genet. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1002\/uog.15754","article-title":"Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome","volume":"47","author":"Gross","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/pd.4333","article-title":"Chromosomal microarray analysis allows prenatal detection of low level mosaic autosomal aneuploidy","volume":"34","author":"Hall","year":"2014","journal-title":"Prenat. Diagn."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1038\/gim.2018.24","article-title":"Patterns of homozygosity in patients with uniparental disomy: Detection rate and suggested reporting thresholds for SNP microarrays","volume":"20","author":"Hoppman","year":"2018","journal-title":"Genet. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"516.e1","DOI":"10.1016\/j.ajog.2020.10.039","article-title":"Prenatal chromosomal microarray analysis in\u00a02466\u00a0fetuses with ultrasonographic soft markers: a\u00a0prospective cohort study","volume":"224","author":"Hu","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12920-018-0410-6","article-title":"Strategies to minimize false positives and interpret novel microdeletions based on maternal copy-number variants in 87, 000 noninvasive prenatal screens","volume":"11","author":"Kaseniit","year":"2018","journal-title":"BMC Med. Genomics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-010-0920-6","article-title":"Regions of homozygosity and their impact on complex diseases and traits","volume":"129","author":"Ku","year":"2011","journal-title":"Hum. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1097\/AOG.0000000000000325","article-title":"Genomic imbalance in products of conception: Single-nucleotide polymorphism chromosomal microarray analysis","volume":"124","author":"Levy","year":"2014","journal-title":"Obstet. Gynecol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1038\/s41436-019-0467-4","article-title":"Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes","volume":"21","author":"Liang","year":"2019","journal-title":"Genet. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1755-8166-3-8","article-title":"Cytogenetic contribution to uniparental disomy (UPD)","volume":"3","author":"Liehr","year":"2010","journal-title":"Mol. Cytogenet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/uog.21951","article-title":"Absence of heterozygosity detected by single-nucleotide polymorphism array in prenatal diagnosis","volume":"57","author":"Liu","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1097\/GIM.0b013e3181f8baad","article-title":"Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities","volume":"12","author":"Manning","year":"2010","journal-title":"Genet. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/ajmg.c.31505","article-title":"Confined placental mosaicism and its impact on confirmation of NIPT results.","volume":"172","author":"Mardy","year":"2016","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"B32","volume-title":"An international system for human cytogenomic nomenclature","author":"McGowan-Jordan","year":"2020"},{"key":"B33","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1097\/GIM.0b013e3182368a0e","article-title":"DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study","volume":"13","author":"Palomaki","year":"2011","journal-title":"Genet. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"691.e1","DOI":"10.1016\/j.ajog.2017.10.005","article-title":"Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory","volume":"217","author":"Petersen","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e0193476","DOI":"10.1371\/journal.pone.0193476","article-title":"Validation of a SNP-based non-invasive prenatal test to detect the fetal 22q11.2 deletion in maternal plasma samples","volume":"13","author":"Ravi","year":"2018","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of medical genetics and genomics (ACMG) and the clinical genome resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<452:AID-BIES7>3.0.CO;2-K","article-title":"Mechanisms leading to uniparental disomy and their clinical consequences","volume":"22","author":"Robinson","year":"2000","journal-title":"Bioessays"},{"key":"B39","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/pd.4710","article-title":"Current controversies in prenatal diagnosis 1: Should NIPT routinely include microdeletions\/microduplications?","volume":"36","author":"Rose","year":"2016","journal-title":"Prenat. Diagn."},{"key":"B40","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/GIM.0b013e3181cc75d0","article-title":"Detection of low-level mosaicism and placental mosaicism by oligonucleotide array comparative genomic hybridization","volume":"12","author":"Scott","year":"2010","journal-title":"Genet. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1002\/pd.1970141304","article-title":"Confined placental mosaicism","volume":"14","author":"Simoni","year":"1994","journal-title":"Prenat. Diagn."},{"key":"B42","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1093\/humupd\/dmu016","article-title":"The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans","volume":"20","author":"Taylor","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e010002","DOI":"10.1136\/bmjopen-2015-010002","article-title":"Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, edwards and patau syndromes: A systematic review and meta-analysis","volume":"6","author":"Taylor-Phillips","year":"2016","journal-title":"BMJ Open"},{"key":"B44","doi-asserted-by":"publisher","first-page":"400","DOI":"10.2353\/ajpath.2006.060161","article-title":"Trophoblastic oxidative stress and the release of cell-free feto-placental DNA","volume":"169","author":"Tjoa","year":"2006","journal-title":"Am. J. Pathol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"332.e1","DOI":"10.1016\/j.ajog.2014.11.041","article-title":"Expanding the scope of noninvasive prenatal testing: Detection of fetal microdeletion syndromes","volume":"212","author":"Wapner","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B46","doi-asserted-by":"publisher","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":"B47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13039-019-0424-6","article-title":"Analytical validation and chromosomal distribution of regions of homozygosity by oligonucleotide array comparative genomic hybridization from normal prenatal and postnatal case series","volume":"12","author":"Wen","year":"2019","journal-title":"Mol. Cytogenet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1146\/annurev-med-091014-115715","article-title":"Prenatal diagnosis innovation: Genome sequencing of maternal plasma","volume":"67","author":"Wong","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/ajmg.c.30270","article-title":"Uniparental disomy and human disease: An overview","author":"Yamazawa","year":"2010","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/uog.22021","article-title":"Clinical utility of expanded non-invasive prenatal screening and chromosomal microarray analysis in high-risk pregnancy","volume":"57","author":"Zhu","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.955694\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T07:45:40Z","timestamp":1664178340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.955694\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":50,"alternative-id":["10.3389\/fgene.2022.955694"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.955694","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]},"article-number":"955694"}}