{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:21:06Z","timestamp":1793910066446,"version":"4.8.0"},"reference-count":10,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ system anomalies. Genes in the BRG1(BRM)-associated factors (BAF, Brahma associated factor) complex have been shown to be causative, including ARID1A, ARID1B, ARID2, DPF2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, and SOX4. In order to describe more robust genotype-phenotype correlations, we collected data from 208 individuals from the CSS\/BAF complex registry with pathogenic variants in seven of these genes. Data were organized into cohorts by affected gene, comparing genotype groups across a number of binary and quantitative phenotypes. We determined that, while numerous phenotypes are seen in individuals with variants in the BAF complex, hypotonia, hypertrichosis, sparse scalp hair, and hypoplasia of the distal phalanx are still some of the most common features. It has been previously proposed that individuals with ARID-related variants are thought to have more learning and developmental struggles, and individuals with SMARC-related variants, while they also have developmental delay, tend to have more severe organ-related complications. SOX-related variants also have developmental differences and organ-related complications but are most associated with neurodevelopmental differences. While these generalizations still overall hold true, we have found that all individuals with BAF-related conditions are at risk of many aspects of the phenotype, and management and surveillance should be broad.<\/jats:p>","DOI":"10.3390\/genes12060937","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T22:00:02Z","timestamp":1624226402000},"page":"937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Ashley","family":"Vasko","sequence":"first","affiliation":[{"name":"Clinical Research Unit, Children\u2019s Hospital of The King\u2019s Daughters, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-0111","authenticated-orcid":false,"given":"Theodore G.","family":"Drivas","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Genetics, The University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-0644","authenticated-orcid":false,"given":"Samantha A.","family":"Schrier Vergano","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism, Children\u2019s Hospital of The King\u2019s Daughters, Norfolk, VA 23507, USA"},{"name":"Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ajhg.2018.12.014","article-title":"De novo SOX4 variants cause a neurodevelopmental disease associated with mild dysmorphism","volume":"104","author":"Zawerton","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fnmol.2018.00252","article-title":"Mutations Landscapes and Phenotypic Spectrum of SWI\/SNF-Related Intellectual Disability Disorders","volume":"11","author":"Wollnik","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1093\/hmg\/ddt366","article-title":"A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling","volume":"22","author":"Wieczorek","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/ajmg.c.31407","article-title":"Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A","volume":"166C","author":"Kosho","year":"2014","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/ajmg.c.31414","article-title":"The ARID1B phenotype: What we have learned so far","volume":"166C","author":"Santen","year":"2014","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1038\/ncomms5011","article-title":"De novo SOX11 mutations cause Coffin-Siris syndrome","volume":"5","author":"Tsurusaki","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/jmedgenet-2015-103393","article-title":"Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome","volume":"53","author":"Hempel","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_8","unstructured":"Vergano, S., Santen, G., Wieczorek, D., Wollnik, B., Matsumoto, N., and Deardorff, M. (2018). Coffin siris syndrome. Gene Reviews, University of Washington."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.ajhg.2018.01.014","article-title":"Mutations in the BAF-complex subunit DPF2 are associated with Coffin-Siris syndrome","volume":"102","author":"Vasileiou","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/s41593-017-0013-0","article-title":"Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior","volume":"20","author":"Jung","year":"2017","journal-title":"Nat. Neurosci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/937\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:19:01Z","timestamp":1760163541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/6\/937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,19]]},"references-count":10,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["genes12060937"],"URL":"https:\/\/doi.org\/10.3390\/genes12060937","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,19]]}}}