{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:13:53Z","timestamp":1792804433603,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T00:00:00Z","timestamp":1557792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Wellcome Sanger Institute","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"https:\/\/ror.org\/05cy4wa09","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome and the Department of Health"},{"name":"Health Innovation Challenge Fund","award":["HICF-1009-003"],"award-info":[{"award-number":["HICF-1009-003"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Variants in the chromodomain helicase DNA\u2010binding protein 8 (CHD8) have been associated with intellectual disability (ID), autism spectrum disorders (ASDs) and overgrowth and CHD8 is one of the causative genes for OGID (overgrowth and ID). We investigated 25 individuals with CHD8 protein truncating variants (PTVs), including 10 previously unreported patients and found a male to female ratio of 2.7:1 (19:7) and a pattern of common features: macrocephaly (62.5%), tall stature (47%), developmental delay and\/or intellectual disability (81%), ASDs (84%), sleep difficulties (50%), gastrointestinal problems (40%), and distinct facial features. Most of the individuals in this cohort had moderate\u2010to\u2010severe ID, some had regression of speech (37%), seizures (27%) and hypotonia (27%) and two individuals were non\u2010ambulant. Our study shows that haploinsufficiency of CHD8 is associated with a distinctive OGID syndrome with pronounced autistic traits and supports a sex\u2010dependent penetrance of CHD8 PTVs in humans.<\/jats:p>","DOI":"10.1111\/cge.13554","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T22:34:52Z","timestamp":1555626892000},"page":"72-84","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The clinical presentation caused by truncating\n                    <i>CHD8<\/i>\n                    variants"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-7544","authenticated-orcid":false,"given":"Sofia","family":"Douzgou","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre  Manchester UK"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Wen","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre  Manchester UK"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Somarathi","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Tischkowitz","sequence":"additional","affiliation":[{"name":"Academic Department of Medical Genetics, Cambridge University Hospitals NHS Foundation Trust University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafik","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha","family":"Kini","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"McKee","sequence":"additional","affiliation":[{"name":"Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust Belfast City Hospital  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Yates","sequence":"additional","affiliation":[{"name":"West of Scotland Regional Genetics Service, NHS Greater Glasgow and Clyde Institute of Medical Genetics, Yorkhill Hospital  Glasgow UK"},{"name":"KwaZulu\u2010Natal Research and Innovation Sequencing Platform (KRISP) University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bertoli","sequence":"additional","affiliation":[{"name":"West of Scotland Regional Genetics Service, NHS Greater Glasgow and Clyde Institute of Medical Genetics, Yorkhill Hospital  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally Ann","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Temple Street Children's Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Holder","sequence":"additional","affiliation":[{"name":"North West Thames Regional Genetics Service  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Deciphering Developmental Disorders Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Banka","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre  Manchester UK"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00322-08"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.07.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp101"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1161"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.01.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06409-11"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11689-011-9083-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.11.005"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1831"},{"key":"e_1_2_8_11_1","unstructured":"The National Institute of Mental Health. Autism spectrum disorder;2016.https:\/\/www.nimh.nih.gov\/health\/topics\/autism-spectrum-disorders-asd\/index.shtml. Accessed February 8 2019."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61539-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11011"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227764"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.028"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10945"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10989"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.06.017"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36741"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37566"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.02.010"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1980"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7404"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.052"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.03.010"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0561-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19357"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4592"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy058"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0208-z"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.04032.x"},{"key":"e_1_2_8_32_1","article-title":"Growth hormone deficiency as a cause for short stature in Wiedemann\u2010Steiner syndrome","volume":"2018","author":"Stoyle G","year":"2018","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2015.11.012"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.001"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53630-3.00006-3"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0217-y"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3792"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.050823"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36229"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.009"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13554","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13554","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13554","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13554","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T09:50:26Z","timestamp":1694339426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,14]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1111\/cge.13554"],"URL":"https:\/\/doi.org\/10.1111\/cge.13554","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13554\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13554\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13554\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13554\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13554\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13554\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,14]]},"assertion":[{"value":"2019-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}