Molecular characteristics

The SMARCA4 gene encodes a subunit of BAF (SWI/SNF) chromatin remodelling complexes.

All SMARCA4 germline alterations that have been reported until now in Coffin-Siris syndrome patients are non-truncating (either missense or small in-frame deletions) clustered within the highly conserved ATPase/helicase domain, thus suggesting dominant-negative or gain-of-function effects.

In contrast, almost all small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) tumours are due to biallelic germline and/or somatic inactivating (nonsense or frameshift) mutations causing complete loss of SMARCA4/BRG1 expression.