{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T02:51:31Z","timestamp":1775703091943,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>CHD3<\/jats:italic> heterozygous variants are associated with Snijders Blok\u2010Campeau syndrome (SBCS) which consists of intellectual disability (ID), macrocephaly, and dysmorphic facies. Most reported variants are missense or loss of function clustered within the ATPase\/helicase domain of the protein. We report a severe neurocognitive phenotype caused by biallelic <jats:italic>CHD3<\/jats:italic> variants in two siblings, each inherited from a mildly affected parent. Male and female siblings were referred to the Genetics Clinic due to severe ID and profound dysmorphism. The parents are first cousins of Iranian descent with borderline intellectual abilities. Exome sequencing was performed for the affected female and her parents. A single homozygous candidate variant in the <jats:italic>CHD3<\/jats:italic> gene was detected in the proband: c.5384_5389dup. p.Arg1796_Phe1797insTrpArg, resulting in an in\u2010frame insertion of 2 amino acids located outside the ATPase\/helicase domain at the C\u2010terminal region of <jats:italic>CHD3<\/jats:italic>\u2010encoding residues. This variant is classified as likely pathogenic according to ACMG guidelines. The variant was detected in a heterozygous state in each parent. Both affected siblings were homozygous, while their unaffected brother did not carry the variant. Biallelic <jats:italic>CHD3<\/jats:italic> variants cause a severe neurodevelopmental syndrome that is distinguishable from SBCS. We assume that the variant type (in\u2010frame insertion) and location may enable <jats:italic>CHD3<\/jats:italic> biallelic variants.<\/jats:p>","DOI":"10.1002\/ajmg.a.63503","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T10:35:10Z","timestamp":1703068510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A severe neurocognitive phenotype caused by biallelic <i>CHD3<\/i> variants in two siblings"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8646-4556","authenticated-orcid":false,"given":"Racheli","family":"Goldfarb Yaacobi","sequence":"first","affiliation":[{"name":"Genetics Institute, Meir Medical Center  Kfar Saba Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rivka","family":"Sukenik Halevy","sequence":"additional","affiliation":[{"name":"Genetics Institute, Meir Medical Center  Kfar Saba Israel"},{"name":"Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2014.05.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104166"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210611"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0654-4"},{"issue":"9","key":"e_1_2_8_7_1","first-page":"965","article-title":"Snijders Blok\u2010Campeau syndrome caused by CHD3 gene mutation: A case report","volume":"23","author":"Fan X. Y.","year":"2021","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.32"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3091"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514326"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.07.012"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.12.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.10.022"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06014-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24088"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.02.014"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T05:39:34Z","timestamp":1719553174000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/ajmg.a.63503"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63503","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"assertion":[{"value":"2023-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63503"}}