The chromatin-remodelling complex SWI/SNF is divided into the two subclasses BAF and PBAF. Mutations in several genes of this chromatin-remodelling complex have been associated with Coffin-Siris Syndrome (ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1 and ARID2).
ARID2 (also referred to as BAF200) encodes for a protein characterized by an AT-rich interaction domain and is expressed in all tissues (Nagase et al., 2000). It was first identified as a PBAF specific subunit regulating the expression of specific interferon-responsive genes (Yan et al., 2005; Bramswig et al., 2017)
Mutations in ARID2 are inherited in an autosomal dominant manner, although mutations in ARID2 are rare and usually occur de novo, i.e. the variant arises for the first time in the affected individual.
All reported patients with intellectual disability had truncating ARID2 mutations or deletions (Bramswig et al., 2017; Shang et al., 2015; Van Paemel et al., 2017). An ARID2 de novo missense variant of unknown significance has been reported in an individual with autism (Iossifov et al., 2014).
Diagnosis/testing
Mutations in ARID2 can be identified using molecular genetic testing, either directly by sequencing and/or MLPA of the ARID2 gene or by exome/genome sequencing.