{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:58:53Z","timestamp":1789923533559,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"French Ministry of Health","award":["PHRC n\u00b02008-A00515-50"],"award-info":[{"award-number":["PHRC n\u00b02008-A00515-50"]}]},{"name":"Regional Council of Burgundy and Dijon University hospital","award":["PARI 2012"],"award-info":[{"award-number":["PARI 2012"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>\n                    Marfanoid habitus (MH) combined with intellectual disability (ID) is a genetically and clinically heterogeneous group of overlapping disorders. We performed exome sequencing in 33 trios and 31 single probands to identify novel genes specific to MH\u2010ID. After the search for variants in known disease\u2010causing genes and non\u2010disease\u2010causing genes with classical approaches, we searched for variants in non\u2010disease\u2010causing genes whose pLI was above 0.9 (ExAC Consortium data), in which truncating variants were found in at least 3 unrelated patients. Only\n                    <jats:italic>DLG4<\/jats:italic>\n                    gene met these criteria. Data from the literature and various databases also indicated its implication in ID.\n                    <jats:italic>DLG4<\/jats:italic>\n                    encodes post\u2010synaptic density protein 95 (PSD\u201095), a protein expressed in various tissues, including the brain. In neurons, PSD\u201095 is located at the post\u2010synaptic density, and is associated with glutamatergic receptor signaling (NMDA and AMPA). PSD\u201095 probably participates in dendritogenesis. Two patients were heterozygous for de novo frameshift variants and one patient carried a a consensus splice site variant. Gene expression studies supported their pathogenicity through haploinsufficiency and loss\u2010of\u2010function. Patients exhibited mild\u2010to\u2010moderate ID, similar marfanoid features, including a long face, high\u2010arched palate, long and thin fingers, pectus excavatum, scoliosis and ophthalmological manifestations (nystagmus or strabismus). Our study emphasizes the role of\n                    <jats:italic>DLG4<\/jats:italic>\n                    as a novel post\u2010synaptic\u2010associated gene involved in syndromic ID associated with MH.\n                  <\/jats:p>","DOI":"10.1111\/cge.13243","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T13:49:04Z","timestamp":1519220944000},"page":"1172-1178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Truncating variants of the\n                    <i>DLG4<\/i>\n                    gene are responsible for intellectual disability with marfanoid features"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-6731","authenticated-orcid":false,"given":"S.","family":"Moutton","sequence":"first","affiliation":[{"name":"Reference Center for Developmental Anomalies, Department of Medical Genetics Dijon University Hospital  Dijon France"},{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-465X","authenticated-orcid":false,"given":"A.\u2010L.","family":"Bruel","sequence":"additional","affiliation":[{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Assoum","sequence":"additional","affiliation":[{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Chevarin","sequence":"additional","affiliation":[{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Sarrazin","sequence":"additional","affiliation":[{"name":"Caribbean Reference Center for Rare Neurological and Neuromuscular Diseases Fort de France University Hospital  Fort de France France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Goizet","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies, Medical Genetics Department, CHU Bordeaux and Laboratoire MRGM, INSERM U1211 University of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.\u2010M.","family":"Guerrot","sequence":"additional","affiliation":[{"name":"Department of Genetics Rouen University Hospital  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Charollais","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine and Intensive Care, Neuropediatrics and Reference Centre for Learning Disabilities Rouen University Hospital  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Charles","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Intellectual Disability Disorders, AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Paris, France and Clinical Research Group \u201cintellectual disability and autism\u201d UPMC  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Heron","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Intellectual Disability Disorders, AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Paris, France and Clinical Research Group \u201cintellectual disability and autism\u201d UPMC  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Faudet","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Intellectual Disability Disorders, AP\u2010HP, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, Paris, France and Clinical Research Group \u201cintellectual disability and autism\u201d UPMC  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Houcinat","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies, Department of Medical Genetics Dijon University Hospital  Dijon France"},{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Vitobello","sequence":"additional","affiliation":[{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Tran\u2010Mau\u2010Them","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies, Department of Medical Genetics Dijon University Hospital  Dijon France"},{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Philippe","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies, Department of Medical Genetics Dijon University Hospital  Dijon France"},{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Duffourd","sequence":"additional","affiliation":[{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Thauvin\u2010Robinet","sequence":"additional","affiliation":[{"name":"Reference Center for Developmental Anomalies, Department of Medical Genetics Dijon University Hospital  Dijon France"},{"name":"INSERM U1231, LNC UMR1231 GAD Burgundy University  Dijon 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