De novo missense mutations in the alternative ATPase subunit BRM are causal for Nicolaides-Baraitser syndrome (NCBRS), a developmental disorder closely related to CSS. NCBRS patients have severe ID, microcephaly, seizures, stunted growth and sparse hair (Nicolaides and Baraitser, 1993); they exhibit enlarged interphalangeal joints rather than hypoplasia of fifth fingernails seen in CSS patients (Sousa et al., 2009). Van Houdt and colleagues found BRM missense mutations in 36/44 (82%) patients with NCBRS (Van Houdt et al., 2012), and additional missense and in-frame deletion mutations were discovered by other groups (Figure 2) (Wolff et al., 2012; Wieczorek et al., 2013; Santen et al., 2013). Interestingly, Wieczorek and colleagues also found 3 truncating mutations in BAF250B and a C-terminal mutation in BAF47 (p.Arg366Cys) (Wieczorek et al., 2013). Similar to the BRG1 mutations in CSS, most BRM mutations are located in the conserved ATPase domain, particularly in the ATP-binding region and the helicase region; this suggests that these missense mutations alter the activity of the ATPase and lead to gain-of-function or dominant negative effects. Given the overall patterns of subunit mutations in CSS
