Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

摘要

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 IlluminaMiseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10 RA, IL-10 RB, NOD2, FUT2, IL23 R, 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-10 RA and IL-10 RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10 RA andFUT2 polymorphisms, and two patients had IL-10 RB 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-10 RA and IL-10 RB 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.