1. Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children
- Author
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Mohmoud Tavassoli, Seyyed Ramin Madani, Mitra Ahmadi, Mina Tabrizi, Shahram Teimourian, Mehri Najafi, Naghi Dara, Farid Imanzadeh, Pejman Rohani, Dirk Roos, Martin de Boer, Taco W. Kuijpers, Maryam Kazemi Aghdam, Shahram Nemati, ARD - Amsterdam Reproduction and Development, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, and Landsteiner Laboratory
- Subjects
Male ,0301 basic medicine ,Interleukin-10 Receptor alpha Subunit ,Iran ,Biology ,medicine.disease_cause ,Inflammatory bowel disease ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Genetics ,medicine ,Humans ,Age of Onset ,Gene ,Genetics (clinical) ,Mutation ,Molecular pathology ,Homozygote ,Heterozygote advantage ,General Medicine ,Inflammatory Bowel Diseases ,Interleukin-10 Receptor beta Subunit ,medicine.disease ,Interleukin-10 ,Interleukin 10 ,030104 developmental biology ,Child, Preschool ,Immunology ,Female ,030211 gastroenterology & hepatology ,Signal Transduction - Abstract
Background & aim: Comparing to adult inflammatory bowel disease (IBD), those with early onset manifestations have different features in terms of the underlying molecular pathology, the course of disease and the response to therapy. We investigated the IL-10 signaling pathway previously reported as an important cause of infantile (Very Early Onset) IBD to find any possible variants. Method: With the next generation sequencing technique we screened IL-10, IL-10RA and IL10RB genes of 15 children affected by very early onset-GI (gastrointestinal) disorders. Additionally, we analyzed them based on Thermo Fisher immune deficiency panel for genes either having a known role in IBD pathogenesis or cause the disorders with overlapping manifestations. We performed multiple functional analyses only for the cases showing variants in IL-10-related genes. Result: In 3 out of 15 patients we identified variants including a homozygous and heterozygote mutations in IL-10RA and a novel homozygous mutation in IL-12RB1. Our functional studies reveal that in contrast to the IL-10RA heterozygote mutation that does not have deleterious effects, the homozygous mutation abrogates the IL-10 signaling pathway. Conclusion: Our study suggests we need to modify the classical diagnostic approach from functional assays followed by candidate-gene or genes sequencing to the firstly parallel genomic screening followed by functional studies. (C) 2017 Elsevier Masson SAS. All rights reserved
- Published
- 2017