Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing

Darrell L. Dinwiddie, Julia M. Bracken, Julie A. Bass, Kathy Christenson, Sarah E. Soden, Carol J. Saunders, Neil A. Miller, Vivekanand Singh, David L. Zwick, Charles C. Roberts, Jignesh Dalal, Stephen F. Kingsmore

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)442-447
Number of pages6
JournalGenomics
Volume102
Issue number5-6
DOIs
StatePublished - Nov 1 2013

Fingerprint

Exome
Inflammatory Bowel Diseases
Siblings
Pediatrics
Failure to Thrive
Mutation
Hematopoietic Stem Cell Transplantation
Exanthema
Abscess
Genes
Morbidity
Safety
Mortality

Keywords

  • Colitis
  • Crohn's disease
  • Exome sequencing
  • Hematopoietic stem cell transplantation
  • IL10
  • IL10RA
  • Inflammatory bowel disease

ASJC Scopus subject areas

  • Genetics

Cite this

Dinwiddie, D. L., Bracken, J. M., Bass, J. A., Christenson, K., Soden, S. E., Saunders, C. J., ... Kingsmore, S. F. (2013). Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing. Genomics, 102(5-6), 442-447. https://doi.org/10.1016/j.ygeno.2013.08.008

Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing. / Dinwiddie, Darrell L.; Bracken, Julia M.; Bass, Julie A.; Christenson, Kathy; Soden, Sarah E.; Saunders, Carol J.; Miller, Neil A.; Singh, Vivekanand; Zwick, David L.; Roberts, Charles C.; Dalal, Jignesh; Kingsmore, Stephen F.

In: Genomics, Vol. 102, No. 5-6, 01.11.2013, p. 442-447.

Research output: Contribution to journalArticle

Dinwiddie, DL, Bracken, JM, Bass, JA, Christenson, K, Soden, SE, Saunders, CJ, Miller, NA, Singh, V, Zwick, DL, Roberts, CC, Dalal, J & Kingsmore, SF 2013, 'Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing', Genomics, vol. 102, no. 5-6, pp. 442-447. https://doi.org/10.1016/j.ygeno.2013.08.008
Dinwiddie DL, Bracken JM, Bass JA, Christenson K, Soden SE, Saunders CJ et al. Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing. Genomics. 2013 Nov 1;102(5-6):442-447. https://doi.org/10.1016/j.ygeno.2013.08.008
Dinwiddie, Darrell L. ; Bracken, Julia M. ; Bass, Julie A. ; Christenson, Kathy ; Soden, Sarah E. ; Saunders, Carol J. ; Miller, Neil A. ; Singh, Vivekanand ; Zwick, David L. ; Roberts, Charles C. ; Dalal, Jignesh ; Kingsmore, Stephen F. / Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing. In: Genomics. 2013 ; Vol. 102, No. 5-6. pp. 442-447.
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