{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:42:01Z","timestamp":1790692921549,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013114","name":"Broad Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["R01 HG009141"],"award-info":[{"award-number":["R01 HG009141"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in <jats:italic>MED12<\/jats:italic>. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well\u2010known syndromes: Opitz\u2013Kaveggia syndrome, Lujan\u2013Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (<jats:italic>p<\/jats:italic>\u00a0=\u20090.993, \u03c7<jats:sup>2<\/jats:sup> test), but mostly outside the functional domains (<jats:italic>p<\/jats:italic>\u00a0=\u20090.004; \u03c7<jats:sup>2<\/jats:sup> test). Statistical analyses did not show a correlation between the <jats:italic>MED12<\/jats:italic>\u2010related phenotypes and the locations of the variants (<jats:italic>p<\/jats:italic>\u00a0=\u20090.295; Pearson correlation), nor the protein domain involved (<jats:italic>p<\/jats:italic>\u00a0=\u20090.422; Pearson correlation). In conclusion, establishing a genotype\u2013phenotype correlation in <jats:italic>MED12<\/jats:italic>\u2010related diseases remains challenging. Therefore, we think that patients with a causative <jats:italic>MED12<\/jats:italic> variant are currently underdiagnosed due to the broad patients' clinical presentations.<\/jats:p>","DOI":"10.1002\/ajmg.a.63004","type":"journal-article","created":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T10:41:13Z","timestamp":1666435273000},"page":"135-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Missense <scp><i>MED12<\/i><\/scp> variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3274-2474","authenticated-orcid":false,"given":"Nuno","family":"Maia","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto); Unit for Multidisciplinary Research In Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), and ITR \u2010 Laboratory for Integrative and Translational Research in Population Health University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nekane","family":"Ibarluzea","sequence":"additional","affiliation":[{"name":"Biocruces Bizkaia Health Research Institute  Barakaldo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Misra\u2010Isrie","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Koboldt","sequence":"additional","affiliation":[{"name":"Steve and Cindy Institute for Genomic Medicine Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"Department of Pediatrics The Ohio State University College of Medicine  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Marques","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto); Unit for Multidisciplinary Research In Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), and ITR \u2010 Laboratory for Integrative and Translational Research in Population Health University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Soares","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica M\u00e9dica Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto)  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros\u00e1rio","family":"Santos","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto de Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto); Unit for Multidisciplinary Research In Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), and ITR \u2010 Laboratory for Integrative and Translational Research in Population Health University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo L. 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