{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:12:39Z","timestamp":1775805159733,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Noninvasive prenatal diagnosis relies on the analysis of the small amount of cell\u2010free fetal DNA circulating in maternal plasma. Widely used to screen for chromosomal anomalies, the technique can also be applied to Mendelian diseases (NIPD\u2010M). However, asserting the presence of a maternal variant in the fetus is challenging and requires the determination of the maternal haplotypes transmitted to the fetus. This is achieved via relative haplotype dosage (RHDO), a method that relies on the analysis of the allelic balance of multiple single\u2010nucleotide polymorphisms around the pathogenic variant. An inherent risk of this method is that twin pregnancies and chromosomal anomalies like trisomy, monosomy or uniparental disomy unavoidably alter allelic balance, potentially leading to incorrect diagnosis. Here, we introduce an analytical method, fetal fraction signatures, that can detect such confounding situations in NIPD\u2010M data, without the need for additional wet\u2010lab work. We show that our method can reliably detect anomalies down to a low level of mosaicism and a low fetal fraction, thereby providing an essential quality\u2010control tool for clinical testing by NIPD\u2010M.<\/jats:p>","DOI":"10.1111\/cge.70121","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:22:27Z","timestamp":1765347747000},"page":"869-875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fetal Fraction Signatures: A Quality Control Tool to Detect Potentially Confounding Situations in NonInvasive Prenatal Diagnosis of Monogenic Conditions"],"prefix":"10.1111","volume":"109","author":[{"given":"Jean\u2010Louis","family":"Blouin","sequence":"first","affiliation":[{"name":"Genetic Medicine, Diagnostic Department Geneva University Hospitals  Geneva Switzerland"},{"name":"Department of Genetic Medicine and Development, Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudine","family":"Rieubland","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Central Institute of the Hospitals Hospital of the Valais  Sion Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-9147","authenticated-orcid":false,"given":"Thierry","family":"Nouspikel","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Diagnostic Department Geneva University Hospitals  Geneva Switzerland"},{"name":"Department of Genetic Medicine and Development, Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13152570"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)02174-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2019.305011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2020.06.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13656"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001720"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14399"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1347290"},{"key":"e_1_2_8_10_1","first-page":"281659","article-title":"smCounter2: An Accurate Low\u2010Frequency Variant Caller for Targeted Sequencing Data With Unique Molecular Identifiers","volume":"14","author":"Xu C.","year":"2018","journal-title":"bioRxiv"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70121","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:24:14Z","timestamp":1775802254000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/cge.70121"],"URL":"https:\/\/doi.org\/10.1111\/cge.70121","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"2025-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}