{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:13:17Z","timestamp":1777626797115,"version":"3.51.4"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Vulto-van Silfhout-de Vries syndrome (VSVS; MIM 615828) is an extremely rare autosomal dominant disorder with unknown incidence. It is always caused by <jats:italic>de novo<\/jats:italic> heterozygous pathogenic variants in the <jats:italic>DEAF1<\/jats:italic> gene, which encodes deformed epidermal autoregulatory factor-1 homology. VSVS is characterized by mild to severe intellectual disability (ID) and\/or global developmental delay (GDD), seriously limited language expression, behavioral abnormalities, somnipathy, and reduced pain sensitivity. In this study, we present a Chinese boy with moderate GDD and ID, severe expressive language impairment, behavioral issues, autism spectrum disorder (ASD), sleeping dysfunction, high pain threshold, generalized seizures, imbalanced gait, and recurrent respiratory infections as clinical features. A <jats:italic>de novo<\/jats:italic> heterozygous pathogenic missense variant was found in the 5th exon of <jats:italic>DEAF1<\/jats:italic> gene, NM_021008.4 c.782G&amp;gt;C (p. Arg261Pro) variant by whole exome sequencing (WES). c.782G&amp;gt;C had not been previously reported in genomic databases and literature. According to the ACMG criteria, this missense variant was considered to be \u201cLikely Pathogenic\u201d. We diagnosed the boy with VSVS both genetically and clinically. At a follow-up of 2.1\u2009years, his seizures were well controlled after valproic acid therapy. In addition, the child\u2019s recurrent respiratory infections improved at 3.5\u2009years of age, which has not been reported in previous individuals. Maybe the recurrent respiratory infections like sleep problems reported in the literature are not permanent but may improve naturally over time. The literature review showed that there were 35 individuals with 28 different <jats:italic>de novo<\/jats:italic> pathogenic variants of <jats:italic>DEAF1<\/jats:italic>-related VSVS. These variants were mostly missense and the clinical manifestations were similar to our patient. Our study expands the genotypic and phenotypic profiles of <jats:italic>de novo DEAF1<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fneur.2023.1251467","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T09:14:45Z","timestamp":1700817285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Vulto-van Silfhout-de Vries syndrome caused by de novo variants of DEAF1 gene: a case report and literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Hui","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zemin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cca.2021.02.026","article-title":"De novo variants of DEAF1 cause intellectual disability in six Chinese patients","volume":"518","author":"Chen","year":"2021","journal-title":"Clin Chim Acta"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1038\/s41436-019-0473-6","article-title":"De novo and biallelic DEAF1 variants cause a phenotypic spectrum","volume":"21","author":"Nabais Sa","year":"2019","journal-title":"Genet Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1097\/MCD.0000000000000252","article-title":"Expanding the phenotype in autosomal dominant mental retardation-24: a novel variation in DEAF1 gene","volume":"28","author":"Sharma","year":"2019","journal-title":"Clin Dysmorphol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1002\/humu.23339","article-title":"Functional analysis of novel DEAF1 variants identified through clinical exome sequencing expands DEAF1-associated neurodevelopmental disorder (DAND) phenotype","volume":"38","author":"Chen","year":"2017","journal-title":"Hum Mutat"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.cca.2018.01.025","article-title":"Two de novo variations identified by massively parallel sequencing in 13 Chinese families with children diagnosed with autism spectrum disorder","volume":"479","author":"Li","year":"2018","journal-title":"Clin Chim Acta"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00439-017-1767-x","article-title":"Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo likely pathogenic variants","volume":"136","author":"Berger","year":"2017","journal-title":"Hum Genet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/gim.2016.88","article-title":"Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers","volume":"19","author":"Wenger","year":"2017","journal-title":"Genet Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ajhg.2014.03.013","article-title":"Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems","volume":"94","author":"Vulto-van Silfhout","year":"2014","journal-title":"Am J Hum Genet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1016\/S0140-6736(12)61480-9","article-title":"Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study","volume":"380","author":"Rauch","year":"2012","journal-title":"Lancet"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/ng.712","article-title":"A de novo paradigm for mental retardation","volume":"42","author":"Vissers","year":"2010","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.3390\/diagnostics12081887","article-title":"A unique observation of a patient with Vulto-van Silfhout-de Vries syndrome","volume":"12","author":"Bodunova","year":"2022","journal-title":"Diagnostics"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1186\/s12887-022-03659-7","article-title":"Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature","volume":"22","author":"Zhu","year":"2022","journal-title":"BMC Pediatr"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1093\/jmcb\/mjs052","article-title":"Reduced DEAF1 function during type 1 diabetes inhibits translation in lymph node stromal cells by suppressing Eif4g3","volume":"5","author":"Yip","year":"2013","journal-title":"J Mol Cell Biol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/1471-213X-8-94","article-title":"Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland","volume":"8","author":"Barker","year":"2008","journal-title":"BMC Dev Biol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/89675","article-title":"The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation[J]","volume":"8","author":"Bottomley","year":"2001","journal-title":"Nat Struct Biol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1251467\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T09:14:47Z","timestamp":1700817287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1251467\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,24]]},"references-count":16,"alternative-id":["10.3389\/fneur.2023.1251467"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1251467","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,24]]},"article-number":"1251467"}}