{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:41:26Z","timestamp":1791348086267,"version":"4.3.1"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Ministry of Education and Research","award":["01GS08161"],"award-info":[{"award-number":["01GS08161"]}]},{"name":"European Union Framework Program 7 (FP7)","award":["241995"],"award-info":[{"award-number":["241995"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat\u2013Kievit\u2013Brunner type, have been described as distinct syndromes with overlapping non\u2010specific features and different missense mutations of the\n                      <jats:italic>MED12<\/jats:italic>\n                      gene have been reported in all of them. We report a family including 10 males and 1 female affected with profound non\u2010specific intellectual disability (ID) which was linked to a 30\u2010cM region extending from Xp11.21 (ALAS2) to Xq22.3 (COL4A5). Parallel sequencing of all X\u2010chromosome exons identified a frameshift mutation (c.5898dupC) of\n                      <jats:italic>MED12<\/jats:italic>\n                      . Mutated mRNA was not affected by non\u2010sense mediated RNA decay and induced an additional abnormal isoform due to activation of cryptic splice\u2010sites in exon 41. Dysmorphic features common to most affected males were long narrow face, high forehead, flat malar area, high nasal bridge, and short philtrum. Language was absent or very limited. Most patients had a friendly personality. Cognitive impairment, varying from borderline to profound ID was similarly observed in seven heterozygous females. There was no correlation between cognitive function and X\u2010chromosome inactivation profiles in blood cells. The severe degree of ID in male patients, as well as variable cognitive impairment in heterozygous females suggests that the duplication observed in the present family may have a more severe effect on MED12 function than missense mutations. In a cognitively impaired male from this family, who also presented with tall stature and dysmorphism and did not have the\n                      <jats:italic>MED12<\/jats:italic>\n                      mutation, a 600\u2010kb duplication at 17p13.3 including the\n                      <jats:italic>YWHAE<\/jats:italic>\n                      gene, was found in a mosaic state. \u00a9 2013 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.36162","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T13:31:35Z","timestamp":1376659895000},"page":"3063-3071","source":"Crossref","is-referenced-by-count":41,"title":["Clinical and neurocognitive characterization of a family with a novel\n                    <i>MED12<\/i>\n                    gene frameshift mutation"],"prefix":"10.1002","volume":"161","author":[{"given":"Gaetan","family":"Lesca","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique and Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Lyon France"},{"name":"INSERM U1028, CNRS UMR5292 Lyon Neuroscience Research Center, TIGER Team University Claude Bernard Lyon 1 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Pierre","family":"Moizard","sequence":"additional","affiliation":[{"name":"INSERM U930 Tours France"},{"name":"Service de G\u00e9n\u00e9tique CHRU de Tours Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Bussy","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence pour les D\u00e9ficiences Intellectuelles Li\u00e9es \u00e0 l'X H\u00f4pital Femme M\u00e8re Enfant Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Boggio","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique and Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan A.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Computational Biology Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Hilger","family":"Ropers","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera M.","family":"Kalscheuer","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Des Portes","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence pour les D\u00e9ficiences Intellectuelles Li\u00e9es \u00e0 l'X H\u00f4pital Femme M\u00e8re Enfant Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Labalme","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique and Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Sanlaville","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique and Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Lyon France"},{"name":"INSERM U1028, CNRS UMR5292 Lyon Neuroscience Research Center, TIGER Team University Claude Bernard Lyon 1 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Edery","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique and Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Lyon France"},{"name":"INSERM U1028, CNRS UMR5292 Lyon Neuroscience Research Center, TIGER Team University Claude Bernard Lyon 1 Universit\u00e9 de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Raynaud","sequence":"additional","affiliation":[{"name":"INSERM U930 Tours France"},{"name":"Service de G\u00e9n\u00e9tique CHRU de Tours Tours 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