{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:49:37Z","timestamp":1793141377255,"version":"4.5.0"},"reference-count":32,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,10,1]]},"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      DYRK1A plays different functions during development, with an important role in controlling brain growth through neuronal proliferation and neurogenesis. It is expressed in a gene dosage dependent manner since\n                      <jats:italic>dyrk1a<\/jats:italic>\n                      haploinsufficiency induces a reduced brain size in mice, and\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      overexpression is the candidate gene for intellectual disability (ID) and microcephaly in Down syndrome. We have identified a 69\u2005kb deletion including the 5\u2032 region of the\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      gene in a patient with growth retardation, primary microcephaly, facial dysmorphism, seizures, ataxic gait, absent speech and ID. Because four patients previously reported with intragenic\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      rearrangements or 21q22 microdeletions including only\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      presented with overlapping phenotypes, we hypothesised that\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      mutations could be responsible for syndromic ID with severe microcephaly and epilepsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      gene was studied by direct sequencing and quantitative PCR in a cohort of 105 patients with ID and at least two symptoms from the Angelman syndrome spectrum (microcephaly &lt; \u22122.5 SD, ataxic gait, seizures and speech delay).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a de novo frameshift mutation (c.290_291delCT; p.Ser97Cysfs*98) in a patient with growth retardation, primary severe microcephaly, delayed language, ID, and seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The identification of a truncating mutation in a patient with ID, severe microcephaly, epilepsy, and growth retardation, combined with its dual function in regulating the neural proliferation\/neuronal differentiation, adds\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      to the list of genes responsible for such a phenotype. ID, microcephaly, epilepsy, and language delay are the more specific features associated with\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      abnormalities.\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      studies should be discussed in patients presenting such a phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101251","type":"journal-article","created":{"date-parts":[[2012,10,25]],"date-time":"2012-10-25T21:51:42Z","timestamp":1351201902000},"page":"731-736","source":"Crossref","is-referenced-by-count":129,"title":["The\n                    <i>DYRK1A<\/i>\n                    gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy"],"prefix":"10.1136","volume":"49","author":[{"given":"Jean-Beno\u00eet","family":"Courcet","sequence":"first","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Anomalies de D\u00e9veloppement et Syndromes Malformatifs de l'interr\u00e9gion Grand-Est, H\u00f4pital d'Enfants, CHU, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Malzac","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, Laboratoire de g\u00e9n\u00e9tique mol\u00e9culaire, CHU de Marseille, H\u00f4pital de la Timone, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Masurel-Paulet","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Anomalies de D\u00e9veloppement et Syndromes Malformatifs de l'interr\u00e9gion Grand-Est, H\u00f4pital d'Enfants, CHU, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Lopez","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Callier","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Laboratoire de Cytog\u00e9n\u00e9tique, Plateau Technique de Biologie, CHU de Dijon, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Lambert","sequence":"additional","affiliation":[{"name":"Service de m\u00e9decine infantile III et de g\u00e9n\u00e9tique clinique, Laboratoire de g\u00e9n\u00e9tique, Unit\u00e9 de g\u00e9n\u00e9tique du service n\u00e9onatale, Maternit\u00e9 r\u00e9gionale de Nancy, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Lemesle","sequence":"additional","affiliation":[{"name":"Service de Neurologie et Laboratoire d'exploration du syst\u00e8me nerveux, H\u00f4pital g\u00e9n\u00e9ral, CHU, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Thevenon","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Anomalies de D\u00e9veloppement et Syndromes Malformatifs de l'interr\u00e9gion Grand-Est, H\u00f4pital d'Enfants, CHU, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Gigot","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Plateau Technique de Biologie, CHU, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Duplomb","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Ragon","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Laboratoire de Cytog\u00e9n\u00e9tique, Plateau Technique de Biologie, CHU de Dijon, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Marle","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente GAD EA 4271 (G\u00e9n\u00e9tique des Anomalies du d\u00e9veloppement), IFR Sant\u00e9 STIC, Universit\u00e9 de Bourgogne, Dijon, France"},{"name":"Laboratoire de Cytog\u00e9n\u00e9tique, Plateau Technique de Biologie, CHU de Dijon, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laure","family":"Mosca-Boidron","sequence":"additional","affiliation":[{"name":"Equipe \u00e9mergente 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