RESUMO
BACKGROUND: Infantile-onset inflammatory bowel disease (IOIBD) is a gastrointestinal inflammatory condition often associated with monogenic disorders and is frequently caused by Interleukin-10 deficiencies. This study aimed to identify the mutation responsible for IBD in an 8-year-old patient from an Iranian family with consanguineous parents. METHODS: Whole-exome sequencing (WES) was employed to identify disease-causing variations. Furthermore, we utilized integrated experimental data of HADDOCK molecular docking platform, including NMR spectroscopy, to characterize the mutant protein and elucidate the underlying functional mechanism of the identified mutation's pathogenicity. RESULTS: Our findings revealed a novel 19-bp deletion mutation (c.25_43del, p.Leu9CysfsTer15) in the IL10RB gene. Sanger sequencing confirmed that this variant was inherited in homozygous state within this family, marking the first mutation identified in exon 1 of this gene. Molecular docking simulation demonstrated that the mutant form of IL10RB exhibited reduced affinity for binding to the Interleukin-10 ligand, leading to disruptions in downstream cellular signaling pathways. CONCLUSIONS: The identification of this novel genetic variant as a causative factor for IOIBD highlights the clinical value of utilizing genetic testing, such as WES, as a reliable diagnostic approach for patients affected by this condition.
