title: Mutations in Interleukin-10 Receptor and Clinical Phenotypes in Patients with Very Early Onset Inflammatory Bowel Disease: A Chinese VEO-IBD Collaboration Group Survey.
abstract: Interleukin-10 (IL10) signaling plays an important role in the pathogenesis of very early onset inflammatory bowel disease (VEO-IBD) in children. However, little is known about the role of the IL10 axis in children with VEO-IBD in China.
  
  
  
  The Chinese VEO-IBD Collaboration Group was created to collect clinical and genetic data from patients deficient in IL10 and the IL10 receptor. High-throughput sequencing was performed to identify mutations in these genes.
  
  
  
  We identified 32 compound heterozygous mutations and 9 homozygous mutations in IL10 receptor subunit alpha and 1 homozygous mutation in IL10 receptor subunit beta. Among these mutations, 10 novel mutations were identified, and 6 pathogenic mutations had been previously described. In patients with IL10 receptor subunit alpha mutations, c.301C>T (p.R101RW) and c.537 G>A (p.T179T) were the most common mutations. For 88.1% of the patients, the initial symptom was diarrhea, with a time of onset of 10.4 ± 8.0 days. Oral ulcers were the first symptom in 23.8% of the patients, with a time of onset of 9.7 ± 2.8 days. Extraintestinal manifestations included perianal abscesses (22/42), perianal fistulas (23/42), oral ulcers (20/42), and recurrent eczema (15/42). Twelve patients underwent enterostomy. These patients also had lower average Z scores in height-for-age and weight-for-age. Various treatment strategies were used, including fecal microbiota transplantation; however, only hematopoietic stem cell transplantation was efficacious.
  
  
  
  This study identified genotypes and phenotypes of Chinese VEO-IBD infants with IL10 receptor mutations. Our study expands the current knowledge on the involvement of the IL10 axis in patients with VEO-IBD.
authors.affiliation: *Department of Gastroenterology and Inflammatory Bowel Disease Center, Children's Hospital of Fudan University, Shanghai, China; †Department of Gastroenterology, Children's Hospital of Zhengzhou, Zhengzhou, China; ‡Department of Gastroenterology, Children's Hospital of Hebei Province, Shijiazhuang, China; §Department of Gastroenterology, Children's Hospital of Hunan Province, Changsha, China; ‖Department of Neonatology, the First Hospital of Zhengzhou University, Zhengzhou, China; ¶Department of Gastroenterology, the First Hospital of Jilin University, Jilin Province, Changchun, China; **Molecular Genetic Diagnosis Center, Shanghai Key Lab Birth Defects, Pediatric Research Institute, Children's Hospital of Fudan University, Shanghai, China; and ††Department of Immunology and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Huang
authors.forename: Kaiyue
authors.initials: K
authors.lastname: Peng
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Li
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Zhao
authors.forename: Jieyu
authors.initials: J
authors.lastname: You
authors.forename: Xiuyong
authors.initials: X
authors.lastname: Cheng
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wu
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Huasong
authors.initials: H
authors.lastname: Zeng
authors.forename: Zhuowen
authors.initials: Z
authors.lastname: Yu
authors.forename: Cuifang
authors.initials: C
authors.lastname: Zheng
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: C081846:IL10RB protein, human; D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit