{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:42:06Z","timestamp":1784054526005,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T00:00:00Z","timestamp":1434326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>De novo mutations (DNM) in <jats:italic>SYNGAP1<\/jats:italic>, encoding Ras\/Rap GTPase\u2010activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with <jats:italic>SYNGAP1<\/jats:italic> DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi\u2010gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss\u2010of\u2010function (3 nonsense; 3 frameshift; 1 whole gene deletion). The remaining two mutations, one of which affected the monozygotic twins, were missense variants. Each individual carrying a DNM in <jats:italic>SYNGAP1<\/jats:italic> had moderate\u2010to\u2010severe ID and 7\/10 had epilepsy; typically myoclonic seizures, absences or drop attacks. 8\/10 had hypotonia, 5\/10 had significant constipation, 7\/10 had wide\u2010based\/unsteady gait, 3\/10 had strabismus, and 2\/10 had significant hip dysplasia. A proportion of the affected individuals had a similar, myopathic facial appearance, with broad nasal bridge, relatively long nose and full lower lip vermilion. A distinctive behavioral phenotype was also observed with aggressive\/challenging behavior and significant sleep problems being common. 7\/10 individuals had MR imaging of the brain each of which was reported as normal. The clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for <jats:italic>SYNGAP1<\/jats:italic> is responsible for both disorders. \u00a9 2015 The Authors. <jats:italic>American Journal of Medical Genetics Part A<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37189","type":"journal-article","created":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T12:15:13Z","timestamp":1434370513000},"page":"2231-2237","source":"Crossref","is-referenced-by-count":117,"title":["De novo, heterozygous, loss\u2010of\u2010function mutations in <i>SYNGAP1<\/i> cause a syndromic form of intellectual disability"],"prefix":"10.1002","volume":"167","author":[{"given":"Michael J.","family":"Parker","sequence":"first","affiliation":[{"name":"Sheffield Children's Hospital NHS Foundation Trust Western Bank Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E.","family":"Fryer","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department Alder Hey Children's NHS Foundation Trust Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Shears","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Churchill Hospital Oxford University Hospitals NHS Trust Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Lachlan","sequence":"additional","affiliation":[{"name":"Wessex Clinical Genetics Service University Hospitals Southampton Southampton UK"},{"name":"Human Genetics and Genomic Medicine Faculty of Medicine, University of Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane A.","family":"McKee","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Belfast City Hospital Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex C.","family":"Magee","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine Belfast City Hospital Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehla","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Guy's and St. Thomas' Hospital NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep C.","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, University Hospitals of Leicester NHS Trust Leicester Royal Infirmary Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo\u2010Mi","family":"Park","sequence":"additional","affiliation":[{"name":"East Anglian Medical Genetics Service, Clinical Genetics Cambridge University Hospitals NHS Foundation Trust Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Benoit","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique Humaine Institut de Pathologie et de G\u00e9n\u00e9tique (I.P.G.) 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