{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:27:45Z","timestamp":1773030465806,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs.<\/jats:p>","DOI":"10.3390\/genes13122389","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T06:58:29Z","timestamp":1671433109000},"page":"2389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies"],"prefix":"10.3390","volume":"13","author":[{"given":"Seher","family":"Basaran","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"},{"name":"Center for Genetic Diagnosis and Research PREMED, Istanbul 34394, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Recep","family":"Has","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim Halil","family":"Kalelioglu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-9429","authenticated-orcid":false,"given":"Tugba","family":"Sarac Sivrikoz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-0176","authenticated-orcid":false,"given":"Birsen","family":"Karaman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"},{"name":"Child Health Institute, Department of Pediatric Basic Sciences, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melike","family":"Kirgiz","sequence":"additional","affiliation":[{"name":"Center for Genetic Diagnosis and Research PREMED, Istanbul 34394, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahir","family":"Dehgan","sequence":"additional","affiliation":[{"name":"Center for Genetic Diagnosis and Research PREMED, Istanbul 34394, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-5916","authenticated-orcid":false,"given":"Tugba","family":"Kalayci","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-6689","authenticated-orcid":false,"given":"Bilge","family":"Ozsait Selcuk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Miny","sequence":"additional","affiliation":[{"name":"Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, CH-4031 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atil","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/gim.2013.29","article-title":"ACMG statement on noninvasive prenatal screening for fetal aneuploidy","volume":"15","author":"Gregg","year":"2013","journal-title":"Genet. 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