OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spf ash mice, and govern susceptibility to RNA-based therapies.

Subtle intronic variations explain species-specific OTC splicing patterns driven by the c.386G>A mutation, and the responsiveness to engineered U1snRNAs, which suggests careful elucidation of molecular mechanisms before proposing translation of tailored therapeutics from animal models to humans.