A Synonymous Variant in IL10RA Affects RNA Splicing in Paediatric Patients with Refractory Inflammatory Bowel Disease

Interleukin-10 receptor ( IL10R ) mutations are associated with severe childhood inflammatory bowel disease (IBD). Two unrelated patients who died of very early-onset severe IBD and sepsis were identified to harbor the same compound heterozygous mutations in IL10RA (p.R101W; p.T179T). A third patient was found to be homozygous for p.T179T. The missense change of p.R101W has been reported. The synonymous change of p.T179T, with a minor allele frequency of 0.035% in the population, was novel. The p.T179T mutation was located before the 5? splice donor site, leading to exon skipping and out-of-frame fusion of exons 3 and 5, causing altered STAT3 phosphorylation in IL10-induced peripheral blood mononuclear cells. The patient developed colitis at six years of age, the oldest reported age of onset among patients with IL10RA mutations, and did not suffer from perianal disease. We report three pediatric patients with a rare, synonymous p.T179T variant causing a splicing error in IL10RA .