A novel nonsense variant in ARID1B causing simultaneous RNA decay and exon skipping is associated with Coffin-Siris syndrome

Coffin-Siris syndrome: New mutation implicated Genomic sequencing has revealed a new causative mutation for Coffin-Siris syndrome (CSS), a very rare disease characterized by developmental delays, intellectual disability and various anatomical abnormalities. A team from Japan led by Takanobu Otomo of Kawasaki Medical School in Kurashiki performed genetic sequencing on a young boy who showed many hallmark features of CSS. The researchers identified a previously undescribed mutation in ARID1B, a gene previously linked to the disease. The mutation introduced a premature stop signal into the ARID1B gene transcript. The boy’s cells responded to the genetic defect by activating two kinds of RNA surveillance mechanisms: one that helped eliminate the faulty transcript, and another designed to alter splicing patterns. The findings could help the medical community diagnosis other cases of CSS and ultimately find treatments.