title: Interleukin-10 receptor mutations in children with neonatal-onset Crohn's disease and intractable ulcerating enterocolitis.
abstract: Neonatal-onset inflammatory bowel disease (IBD) accounts for only 0.25% of pediatric IBD cases. The molecular pathogenesis of IBD remains unclear. Recently, rare Mendelian mutations have been identified in children with very early-onset Crohn's disease and ulcerative colitis. In this study, we report compound heterozygous mutations in the interleukin-10 receptor A (IL-10RA) gene in children with severe neonatal-onset IBD. Patient 1 had chronic diarrhea within the first month of life and had perianal fistulae. She was diagnosed with 'intractable ulcerating enterocolitis in infancy' and underwent subtotal colectomy at the age of 24 months because of poor response to immunosuppressant therapy. Compound heterozygous mutations, c.[301C>T];[350G>A](p.[R101W];[R117H]), were discovered in IL-10RA for this patient. Patient 2 presented symptoms within the first month of life and was diagnosed with Crohn's disease. Severe colitis and perianal and enteroenteric fistulae occurred repeatedly, and he underwent surgical management involving colectomy, colostomy, and ileostomy. We identified mutations in IL-10RA, c.[272A>G];[784C>T] (p.[Y91C];[R262C]). Patient 3 had chronic diarrhea and a rectovaginal fistula at 3 days of life and was diagnosed with Crohn's disease. She underwent fistulectomy and ileostomy, but experienced frequent relapses. Mutations, c.[272A>G];[301C>T] (p.[Y91C];[R101W]), were found in IL-10RA. This report confirms the genetic defect of IL-10RA in neonatal-onset IBD including 'intractable ulcerating enterocolitis in infancy'.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Shim
authors.forename: Solha
authors.initials: S
authors.lastname: Hwang
authors.forename: Hye Ran
authors.initials: HR
authors.lastname: Yang
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Moon
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Chang
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Ko
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.forename: Gyeong-Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Woo Sun
authors.initials: WS
authors.lastname: Kim
authors.forename: Jeong Kee
authors.initials: JK
authors.lastname: Seo
mesh_terms: D003093:Colitis, Ulcerative / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D003113:Colonoscopy; D003424:Crohn Disease / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation
chemical_list: D053709:Interleukin-10 Receptor alpha Subunit