Coffin-Siris Syndrome-1: Report of five cases from Asian populations with truncating mutations in the ARID1B gene

Background: Pathogenic variants of the ARID1B gene are recognized as the most common cause of Coffin-Siris syndrome (CSS) and also one of the most common causes for intellectual disability (ID). Reported ARID1B variants in association with CSS are mostly from patients of European ancestry.

Methods: We performed next-generation sequencing to identify pathogenic variants in patients with congenital disorders from the Genetics clinics. The identified variants were validated by Sanger sequencing. Parental samples were tested by Sanger sequencing to determine inheritance status.

Results: Truncating variants in ARID1B were identified in five unrelated Asian patients (one Malay, two Chinese and two Indian) with features of CSS. One was a nonsense mutation which had been documented in three other reports while the other four were novel variants, including two nonsense substitutions and two small deletions resulting in premature termination of translation. Similar to previous reports, all patients have developmental and speech delay, with additional presentations such as ectodermal/facial abnormalities commonly observed in CSS patients.

Conclusions: Our results unveil ARID1B variants in association with CSS in multiple Southeast Asian ethnic groups, and confirm that variants associated with this disorder tend to be of the truncating type. This finding may provide additional insight into the function of the protein and the disease mechanism.