Santen et al and Tsurusaki et al are reporting in Nature Genetics that mutations in the SWItch/Sucrose NonFermenting (SWI/SNF) complex are causing Coffin-Siris syndrome. SWI/SNF has important roles in lineage specification, maintenance of stem cell pluripotency and tumorigenesis and there is evidence that it may act as an epigenetic modifier by altering chromatin structure, thereby facilitating the access of transcription factors to DNA. Pathogenic variants were identified six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B. When tested, all mutations were proven to be de novo. As mentioned by Tsurusaki et al, this is yet another example of genes implicated in chromatin remodeling as was the case for ATRX and CHARGE syndromes.
Periklis Makrythanasis, MD, PhD