{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:07:31Z","timestamp":1772082451238,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2B2001054 to BYC"],"award-info":[{"award-number":["2018R1A2B2001054 to BYC"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Health Technology R&amp;D Project","award":["HI17C0952"],"award-info":[{"award-number":["HI17C0952"]}]},{"name":"Institute of Information &amp; communications Technology Planning &amp; evaluation(IITP) grant","award":["2018-0-00861"],"award-info":[{"award-number":["2018-0-00861"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Elongation factor Tu guanosine-5\u2019-triphosphate (GTP) binding domain containing 2 (EFTUD2) encodes a major component of the spliceosomal GTPase and, if mutated, causes mandibulofacial dysostosis with microcephaly (MFDM; MIM#610536). Despite the increasing number of potentially pathogenic variants reported in the literature, most previous studies have relied solely on in silico prediction of the pathogenic potential of EFTUD2 variants, which may result in misclassification of the variant\u2019s pathogenicity. Given the importance of the functional verification of EFTUD2 variants, we identified a novel splice donor site variant, c.271+1G&gt;A of EFTUD2, whose pathogenicity was clearly verified at the RNA level using a minigene assay. A child with MFDM, mixed hearing loss, microcephaly, and a congenital cardiac defect was identified with this variant, which arose in a de novo fashion. The minigene assay showed erroneous integration of the 118 bp IVS3 of EFTUD2 exclusively among the c.271+1G&gt;A variant clone. We first applied the minigene assay to identify the splice function of a splice site variant of EFTUD2, thereby allowing for in vitro functional verification of splice site variants in EFTUD2.<\/jats:p>","DOI":"10.3390\/diagnostics10050296","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T10:53:55Z","timestamp":1589280835000},"page":"296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel Splice Site Pathogenic Variant of EFTUD2 Is Associated with Mandibulofacial Dysostosis with Microcephaly and Extracranial Symptoms in Korea"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7361-4930","authenticated-orcid":false,"given":"So Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-2770","authenticated-orcid":false,"given":"Da-hye","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam 13496, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Yoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam 13496, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/01.mcd.0000220603.09661.7e","article-title":"A new syndrome with growth and mental retardation, mandibulofacial dysostosis, microcephaly, and cleft palate","volume":"15","author":"Vendramini","year":"2006","journal-title":"Clin. 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