Novel de novo mutations of the interleukin-10 receptor gene lead to infantile onset inflammatory bowel disease

Background and aims: Defects in the interleukin 10 (IL-10) signalling pathway have been shown to cause very early onset inflammatory bowel disease (IBD). We report a patient with severe infantile-onset IBD with a compound heterozygous IL-10 receptor alpha subunit (IL-10RA) mutation, one of which was paternally-inherited and the other occurring de novo. Methods: Deep sequencing of IL-10, IL-10RA and IL-10 receptor beta subunit (IL-10RB) were performed. Peripheral blood mononuclear cell (PBMC) surface expression of IL-10RA was analysed by flow cytometry. IL-10 signalling pathway was examined by measuring phosphorylated STAT3 in PBMC cultured in the presence of IL-6 or IL-10. Result: We identified a missense mutation in exon 4 of IL-10RA (c.583T>C) in one allele and a nonsense mutation in exon 7 of IL-10RA (c.1368G>T) in the other allele. Neither mutation has been reported previously. The patient has functional IL-10RA deficiency despite normal IL-10RA expression. Conclusion: This represents the first case report of a de novo mutation of IL-10RA that is associated with very early onset severe IBD. Therefore, IL-10 pathway defect should be considered in patients with infantile-onset IBD even if the parents are non-consanguineous.