Published online Jun 28, 2016. doi: 10.3748/wjg.v22.i24.5578
Peer-review started: February 29, 2016
First decision: March 31, 2016
Revised: April 13, 2016
Accepted: April 20, 2016
Article in press: April 20, 2016
Published online: June 28, 2016
Processing time: 114 Days and 17.1 Hours
AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease (VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients.
METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing (NGS) based on an Illumina-Miseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10RA, IL-10RB, NOD2, FUT2, IL23R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS.
RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn’s disease, and three diagnosed with ulcerative colitis. Mutations in IL-10RA and IL-10RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10RA and FUT2 polymorphisms, and two patients had IL-10RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight (1.0% vs 27.5%, P = 0.002) and hemoglobin (87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups.
CONCLUSION: IL-10RA and IL-10RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis.
Core tip: In this small-sample size study, we performed next generation sequencing for 10 candidate genes in Chinese pediatric patients with very early onset inflammatory bowel disease. We found that IL-10RA and IL-10RB mutations were common. There were five patients harbouring mutations in these two genes and accounted for 38.5% of all samples. Besides, there were four patients who had single nucleotide polymorphisms associated with inflammatory bowel disease. Pediatric patients with mutations had an earlier disease onset, lower body weight, markedly lower hemoglobin, and poorer prognosis.