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Interleukin-10 receptor mutations in children with neonatal-onset Crohn's disease and intractable ulcerating
Jung Ok Shim1, Solha Hwang, Hye Ran Yang
1Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Seoul National University College of Medicine, Seoul, Korea.
Insights
Severe neonatal inflammatory bowel disease (IBD) in infants is linked to mutations in the interleukin-10 receptor A (IL-10RA) gene. This finding clarifies the genetic cause of this rare but serious condition.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Neonatal inflammatory bowel disease (IBD) is rare, comprising only 0.25% of pediatric cases.
- The molecular basis of IBD, particularly in its earliest forms, remains incompletely understood.
- Recent research has implicated rare Mendelian mutations in very early-onset IBD.
Observation:
- This study investigated three infants with severe, early-onset IBD.
- All patients presented with chronic diarrhea and complex fistulating disease within the first month of life.
- Two patients were diagnosed with Crohn's disease, and one with intractable ulcerating enterocolitis in infancy.
Findings:
- Compound heterozygous mutations in the interleukin-10 receptor A (IL-10RA) gene were identified in all three patients.
- Specific mutations found include c.[301C>T];[350G>A] (p.[R101W];[R117H]), c.[272A>G];[784C>T] (p.[Y91C];[R262C]), and c.[272A>G];[301C>T] (p.[Y91C];[R101W]).
- These genetic defects confirm IL-10RA's role in the pathogenesis of severe neonatal-onset IBD.
Implications:
- This research highlights IL-10RA mutations as a significant genetic cause of severe neonatal IBD.
- Understanding these genetic underpinnings can aid in earlier diagnosis and targeted therapies for affected infants.
- Further research into IL-10 signaling pathways may reveal new therapeutic strategies for IBD.
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'.
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