Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes

We show that bi-allelic variants in the minor spliceosome snRNAs RNU6ATAC and RNU4ATAC cause early-onset autoimmune diabetes with immune dysregulation. We define a shared mechanism involving U12 intron retention and impaired B cell development, expanding the phenotypic spectrum of RNU4ATAC-opathy and implicating minor splicing in beta cell autoimmunity.