Abstract
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.
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Data availability
No datasets were generated or analysed during the current study.
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Acknowledgements
We extend our gratitude to the patient, their family members, and all study participants for their valuable contributions.
Funding
This study received financial support from Golestan University of Medical Sciences (Grant number: 113339).
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Author contributionFarzaneh Motallebi: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Writing - original draft.Zainab M. Al Sudani: Conceptualization, Methodology, Investigation, Formal analysis, Writing - original draft.Fatemeh Vaghefi: Visualization, Methodology, Formal analysis, Writing - original draft.Teymoor Khosravi: Visualization, Methodology, Formal analysis, Writing - original draft.Arian Rahimzadeh: Methodology, Formal analysis. Ali Kowsari: Methodology.Morteza Oladnabi: Conceptualization, Supervision, Validation, Writing - review & editing.
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Our research adhered to the ethical guidelines outlined by the Ethics Committee of Golestan University of Medical Sciences (Ethics Code: IR.GOUMS.REC.1401.540).
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Motallebi, F., Al Sudani, Z.M., Vaghefi, F. et al. A novel biallelic 19-bp deletion in the IL10RB gene caused infant-onset inflammatory bowel disease in a consanguineous family: a molecular docking simulation study and literature review. Mol Biol Rep 51, 223 (2024). https://doi.org/10.1007/s11033-024-09248-4
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DOI: https://doi.org/10.1007/s11033-024-09248-4