ARID1A was initially reported in relation to Coffin-Siris syndrome (CSS), a condition characterized by varying degrees of intellectual disability, characteristic facial features, atypical hair patterns (sparse scalp hair but hypertrichosis on other areas of the body), and digital abnormalities, in 2012 (PMID: 22426308). At least 14 probands have been reported in the literature; variants were de novo in all subjects with available parental DNA (PMIDs: 23906836, 23929686, 31530938). While most reported variants were truncating variants, at least one missense variant has been reported in an individual with features consistent with CSS (PMID: 31530938). Several of the reported variants have been found to be mosaic in the probands. There is experimental evidence to support this gene-disease relationship, including data showing that ARID1A interacts with proteins in the BRG1-associated factor (BAF) complex; genes encoding for other proteins within this complex, such as ARID1B, SMARCA4, and SMARCB1, have also been associated with CSS (PMID: 32001526). Mice with heterozygous loss of ARID1A in neural crest cells exhibit mild craniofacial defects (PMID: 26806701). In summary, there is definitive evidence supporting a relationship between ARID1A and CSS. This curation was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 2021/07/07 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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