Title

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

Document Type

Article

Publication Date

11-1-2013

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

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