{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:00Z","timestamp":1787028240031,"version":"build-2736575974"},"reference-count":15,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"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>In the present study, an exceptional germline gene fusion involving the protein-coding MN1 gene and the long non-coding RNA (lncRNA) gene CPMER was detected as the genetic cause of severe cerebral abnormalities with unfavorable prognosis in a male fetus at 14 weeks of gestation. Quantitative and qualitative RNA analyses indicate the expression of C-terminally truncated MN1 proteins. MN1 proteins lacking the C-terminal amino acids have been previously described to cause an ultra-rare syndrome with brain malformations due to a gain-of-function effect. To the best of our knowledge, this is the first study reporting a germline gene fusion of a protein-coding gene and an lncRNA gene linked to a functional, but neomorphic, protein associated with severe phenotypic abnormalities. The results of our study are not only relevant for the genotype\u2013phenotype correlation of MN1 but should especially raise awareness for potentially disease-associated protein expressions in germline gene fusions involving lncRNAs.<\/jats:p>","DOI":"10.3390\/genes16050598","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T04:48:18Z","timestamp":1747716498000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Expression of a Germline Fusion Gene Involving a Protein-Coding and a Long Non-Coding RNA Gene Results in Severe Brain Malformations"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-7486","authenticated-orcid":false,"given":"Lukas","family":"Kaufmann","sequence":"first","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Beichler","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Blatterer","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Janisch","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Csap\u00f3","sequence":"additional","affiliation":[{"name":"Division of Obstetrics, Department of Obstetrics and Gynaecology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3924-8814","authenticated-orcid":false,"given":"Elisabeth","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9160-0682","authenticated-orcid":false,"given":"Jochen B.","family":"Geigl","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Windpassinger","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.canlet.2013.01.011","article-title":"Fusion genes and their discovery using high throughput sequencing","volume":"340","author":"Annala","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101136","DOI":"10.1016\/j.gendis.2023.101136","article-title":"Breaking paradigms: Long non-coding RNAs forming gene fusions with potential implications in cancer","volume":"11","year":"2024","journal-title":"Genes Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12618","DOI":"10.1093\/nar\/gkaa1119","article-title":"The landscape of long noncoding RNA-involved and tumor-specific fusions across various cancers","volume":"48","author":"Guo","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_4","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. 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