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Genet."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chromosomal triplications are rare structural variations often associated with complex phenotypes. We report the molecular characterization of a novel intrachromosomal triplication at 18q12.1q21.2 identified in a fetus with ultrasound abnormalities. Conventional karyotyping and array-CGH revealed a partial tetrasomy and a 26\u00a0Mb region of loss of homozygosity (LOH), extending from the triplication to the telomere. Long-read sequencing (LRS) identified breakpoint junctions revealing a direct-inverted-direct triplication structure. Breakpoint analysis suggested that this rearrangement arose through a U-type exchange between sister chromatids, likely mediated by microhomology-based mechanisms. This process likely generated a transient dicentric chromosome that subsequently broke during mitosis. The resulting duplicated chromosome may have been stabilized by telomere capture, consistent with the triplicated 18q12.1q21.2 region followed by the 18q21.2q23 LOH. Nine genes within the triplicated region, including\n                    <jats:italic>SMAD2<\/jats:italic>\n                    and\n                    <jats:italic>SMAD4<\/jats:italic>\n                    , showed high predicted sensitivity to increased dosage, possibly contributing to the clinical phenotype. This study highlights the utility of LRS in defining complex chromosomal rearrangements and emphasizes the importance of molecular breakpoint analysis for understanding pathogenic mechanisms and improving genetic prenatal diagnosis.\n                  <\/jats:p>","DOI":"10.1007\/s00439-026-02855-0","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T06:32:21Z","timestamp":1783146741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-read genome sequencing resolves a de novo complex 18q12.1q21.2 triplication causing partial tetrasomy and reveals its underlying mechanism"],"prefix":"10.1007","volume":"145","author":[{"given":"Serena","family":"Redaelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Tritto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Mangano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bordoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Villa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Crosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Dalpr\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Spaccini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Sirtori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Conconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-846X","authenticated-orcid":false,"given":"Angela","family":"Bentivegna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"issue":"3","key":"2855_CR1","doi-asserted-by":"publisher","first-page":"e63457","DOI":"10.1002\/ajmg.a.63457","volume":"194","author":"A Bourgois","year":"2024","unstructured":"Bourgois A, Bizaoui V, Colson C, Vincent-Devulder A, Molin A, G\u00e9rard M, Gruchy N (2024) Phenotypic and genotypic characterization of 1q21.1 copy number variants: A report of 34 new individuals and literature review. 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