Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2820826 | Genomics | 2013 | 6 Pages |
•We use exome sequencing to diagnose infantile-onset inflammatory bowel disease.•Hematopoietic stem cell transplant produced clinical remission of all IBD symptoms.•We caution that severe viral infection post-transplantation should be considered.•We provide rare variant burden in IL10RA and IL10RB from more than 1300 exomes.
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.