Frameshift Variant in in a Chilean Individual with Coffin-Siris Syndrome Phenotype.

Coffin-Siris syndrome (CSS) is one of the several causes of intellectual disability (ID) and, since its first description, has posed diagnostic challenges given its variability and phenotypic overlap with other alterations of chromatin-remodeling-associated syndromes. It is genetically heterogeneous, and causative mutations are detected in less than 70% of cases. The different subtypes of the syndrome described to date are caused by mutations in genes that encode subunits of the SWI/SNF chromatin-remodeling complex, which plays an essential role in the regulation of gene expression during embryogenesis. Whole exome sequencing (WES) has allowed the identification of pathogenic mutations in these genes, including . is one of the primary components of the SWI/SNF complex and has been associated with ID and phenotypes similar to CSS for the first time in 2015. Fifteen published case reports have identified loss-of-function mutations, suggesting that the underlying pathogenic disease mechanism is haploinsufficiency of . We herein presented the case of an 8-year-old Chilean girl with clinical suspicion of CSS, in whom a novel frameshift variant in was identified by WES. She was the first reported case in Latin America to our knowledge and her phenotype displays the main clinical features suggestive of CSS described in other patients with variants. However, she did not present behavioral abnormalities, a characteristic frequently reported in the majority of patients with variants, and also had some features, such as sparse scalp hair, which is frequently reported as a manifestation of CSS, but is uncommon in this new group of patients.