Very early onset inflammatory bowel disease: Investigation of the IL-10 signaling pathway in Iranian children.
Eur J Med Genet
; 60(12): 643-649, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28864178
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Interleucina-10
/
Subunidade alfa de Receptor de Interleucina-10
/
Subunidade beta de Receptor de Interleucina-10
Tipo de estudo:
Prognostic_studies
Limite:
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article