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We present a female proband with a\n                    <jats:italic>de novo<\/jats:italic>\n                    Chromosome 15 paracentric inversion, disrupting\n                    <jats:italic>MEIS2<\/jats:italic>\n                    and\n                    <jats:italic>NUSAP1<\/jats:italic>\n                    . The inversion was detected by short-read genome sequencing and confirmed with adaptive long-read sequencing. The breakpoint junction analysis revealed a 96\u00a0bp (bp) deletion and an 18\u00a0bp insertion in the two junctions, suggesting that the rearrangement arose through a replicative error. Transcriptome sequencing of cultured fibroblasts revealed normal\n                    <jats:italic>MEIS2<\/jats:italic>\n                    levels and 0.61-fold decreased expression of\n                    <jats:italic>NUSAP1<\/jats:italic>\n                    . Furthermore, three fusion transcripts were detected and confirmed by Sanger sequencing. Heterozygous loss of\n                    <jats:italic>MEIS2\u00a0<\/jats:italic>\n                    (MIM# 600987) is associated with a cleft palate, heart malformations, and intellectual impairment, which overlap with the clinical symptoms observed in the proband. The observed fusion transcripts are likely non-functional, and\n                    <jats:italic>MEIS2<\/jats:italic>\n                    haploinsufficiency is the likely disease causative mechanism. Altogether, this study\u2019s findings illustrate the importance of including inversions in rare disease diagnostic testing and highlight the value of long read sequencing for the validation and characterization of such variants.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-81507-7","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T04:15:36Z","timestamp":1733372136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis detail a submicroscopic inv(15)(q14q15) generating fusion transcripts and MEIS2 and NUSAP1 haploinsufficiency"],"prefix":"10.1038","volume":"14","author":[{"given":"Marlene","family":"Ek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Kvarnung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pettersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Johansson","family":"Soller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britt-Marie","family":"Anderlid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e5kan","family":"Thonberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"Eisfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"issue":"5","key":"81507_CR1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1097-2765(00)80393-7","volume":"4","author":"J Capdevila","year":"1999","unstructured":"Capdevila, J., Tsukui, T., Rodr\u00edquez Esteban, C., Zappavigna, V. & Izpis\u00faa Belmonte, J. 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