title: Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Xin-Qiong
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gong
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Li
authors.affiliation: Yuan Xiao, Xin-Qiong Wang, Yi Yu, Yan Guo, Xu Xu, Ling Gong, Tong Zhou, Chun-Di Xu, Pediatric Department, Ruijin Hospital and Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Chun-Di
authors.initials: CD
authors.lastname: Xu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D051722:ADAM Proteins; D005647:Fucosyltransferases; D016753:Interleukin-10; D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D053473:Nod2 Signaling Adaptor Protein; D043562:Receptors, G-Protein-Coupled; D018123:Receptors, Interleukin; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C111379:GPR35 protein, human; C513334:GPR65 protein, human; C508609:IL10 protein, human; C515500:IL23R protein, human; C429018:NOD2 protein, human; C117026:TNFSF15 protein, human; C122190:ADAM30 protein, human
keywords: FUT2 gene; Interleukin 10 receptor; NOD2 gene; Pediatric inflammatory bowel disease; Very early-onset inflammatory bowel disease