{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:07:04Z","timestamp":1787065624808,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35\u2013100.00%); 100.00% sensitivity for T18 (71.51\u2013100.00%); and 100.00% sensitivity for T13 analyses (66.37\u2013100.00%). The specificities were &gt;99% for each trisomy (99.7% (99.01\u201399.97%) for T21; 99.5% (98.62\u201399.85%) for T18; 99.7% (99.03\u201399.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.<\/jats:p>","DOI":"10.3390\/cimb43020068","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:17:06Z","timestamp":1629235026000},"page":"958-964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology"],"prefix":"10.3390","volume":"43","author":[{"given":"Uzay","family":"Gormus","sequence":"first","affiliation":[{"name":"PerkinElmer Genomics Sweden, 191 38 Sollentuna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0914-9237","authenticated-orcid":false,"given":"Alka","family":"Chaubey","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics, Pittsburgh, PA 15275, USA"},{"name":"Bionano Genomics, San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Shenoy","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics, Pittsburgh, PA 15275, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Wee","family":"Wong","sequence":"additional","affiliation":[{"name":"DNA Laboratories Sdn. Bhd, PerkinElmer Genomics Malaysia, Bangi 43650, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Yin","family":"Chan","sequence":"additional","affiliation":[{"name":"DNA Laboratories Sdn. Bhd, PerkinElmer Genomics Malaysia, Bangi 43650, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Ping","family":"Choo","sequence":"additional","affiliation":[{"name":"DNA Laboratories Sdn. Bhd, PerkinElmer Genomics Malaysia, Bangi 43650, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Oraha","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics Sweden, 191 38 Sollentuna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gousseva","sequence":"additional","affiliation":[{"name":"Vanadis Diagnostics, PerkinElmer Inc., 191 38 Sollentuna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Persson","sequence":"additional","affiliation":[{"name":"Vanadis Diagnostics, PerkinElmer Inc., 191 38 Sollentuna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-9122","authenticated-orcid":false,"given":"Lawrence","family":"Prensky","sequence":"additional","affiliation":[{"name":"PerkinElmer Inc., Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephrem","family":"Chin","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics, Pittsburgh, PA 15275, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Hegde","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics, Pittsburgh, PA 15275, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"ref_1","first-page":"386","article-title":"International variation in reported livebirth prevalence rates of Down syndrome, adjusted for maternal age","volume":"36","author":"Carothers","year":"1999","journal-title":"J. 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