TY - JOUR
T1 - Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children
AU - Nemati, Shahram
AU - Teimourian, Shahram
AU - Tabrizi, Mina
AU - Najafi, Mehri
AU - Dara, Naghi
AU - Imanzadeh, Farid
AU - Ahmadi, Mitra
AU - Aghdam, Maryam Kazemi
AU - Tavassoli, Mohmoud
AU - Rohani, Pejman
AU - Madani, Seyyed Ramin
AU - de Boer, Martin
AU - Kuijpers, T. W.
AU - Roos, Dirk
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.ejmg.2017.08.016
DO - https://doi.org/10.1016/j.ejmg.2017.08.016
M3 - Article
C2 - 28864178
SN - 1769-7212
VL - 60
SP - 643
EP - 649
JO - European journal of medical genetics
JF - European journal of medical genetics
IS - 12
ER -