Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing.

Creator(s)

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

Document Type

Article

Publication Date

11-1-2013

Identifier

10.1016/j.ygeno.2013.08.008

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.

Journal Title

Genomics

Volume

102

Issue

5-6

First Page

442

Last Page

447

MeSH Keywords

Child; Exome; Genetic Testing; Genetic Variation; Hematopoietic Stem Cell Transplantation; Humans; Infant; Inflammatory Bowel Diseases; Interleukin-10 Receptor alpha Subunit; Male; Molecular Diagnostic Techniques; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Treatment Outcome

Keywords

Exome; Genetic Testing; Genetic Variation; Hematopoietic Stem Cell Transplantation; Inflammatory Bowel Diseases; Interleukin-10 Receptor alpha Subunit; Molecular Diagnostic Techniques; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Treatment Outcome

Comments

Grant support

• UL1 TR000041/TR/NCATS NIH HHS/United States

Recommended Citation

Dinwiddie, D. L., Bracken, J. M., Bass, J. A., Christenson, K., Soden, S., Saunders, C. J., Miller, N. A., Singh, V., Zwick, D. L., Roberts, C. C., Dalal, J., Kingsmore, S. F. Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing. Genomics 102, 442-447 (2013).