Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing
Darrell L Dinwiddie1, Julia M Bracken2, Julie A Bass2
1Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO 64108, USA; Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA; Department of Pathology, Children's Mercy Hospital, Kansas City, MO 64108, USA; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; Department of Pediatrics, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA; Clinical Translational Science Center, University of New Mexico, Albuquerque, NM 87131, USA.
Insights
Severe pediatric inflammatory bowel disease (IBD) in two brothers was linked to IL10RA mutations. Hematopoietic stem cell transplantation (HSCT) led to significant clinical improvement, highlighting genetic diagnosis and treatment efficacy.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Pediatric-onset inflammatory bowel disease (IBD) often presents severely with poor therapeutic response and increased mortality.
- Infantile-onset IBD requires early diagnosis and effective management strategies.
Observation:
- Two brothers with severe, early-onset IBD, failure to thrive, skin rash, and perirectal abscesses were studied.
- Exome sequencing identified compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys) in both siblings.
Findings:
- Molecular diagnosis revealed IL10RA mutations as the cause of severe IBD in these siblings.
- The proband experienced successful hematopoietic stem cell transplantation (HSCT), showing marked clinical improvement.
Implications:
- Exome sequencing is a valuable tool for diagnosing pediatric-onset IBD.
- HSCT demonstrates safety and efficacy for IBD patients with IL10RA gene mutations.
Abstract:
Pediatric-onset inflammatory bowel disease (IBD) is known to be associated with severe disease, poor response to therapy, and increased morbidity and mortality. We conducted exome sequencing of two brothers from a non-consanguineous relationship who presented before the age of one with severe infantile-onset IBD, failure to thrive, skin rash, and perirectal abscesses refractory to medical management. We examined the variants discovered in all known IBD-associated and primary immunodeficiency genes in both siblings. The siblings were identified to harbor compound heterozygous mutations in IL10RA (c.784C>T, p.Arg262Cys; c.349C>T, p.Arg117Cys). Upon molecular diagnosis, the proband underwent successful hematopoietic stem cell transplantation and demonstrated marked clinical improvement of all IBD-associated clinical symptoms. Exome sequencing can be an effective tool to aid in the molecular diagnosis of pediatric-onset IBD. We provide additional evidence of the safety and benefit of HSCT for patients with IBD due to mutations in the IL10RA gene.
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