title: Molecular diagnosis of infantile onset inflammatory bowel disease by exome sequencing.
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.
authors.affiliation: Center 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. Electronic address: dldinwiddie@salud.unm.edu.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Dinwiddie
authors.affiliation: Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO 64108, USA. Electronic address: jmbracken@cmh.edu.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Bracken
authors.affiliation: Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO 64108, USA. Electronic address: jabass@cmh.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bass
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO 64108, USA; Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO 64108, USA. Electronic address: kchristenson@cmh.edu.
authors.forename: Kathy
authors.initials: K
authors.lastname: Christenson
authors.affiliation: Center 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; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA. Electronic address: ssoden@cmh.edu.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Soden
authors.affiliation: Center 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. Electronic address: csaunders@cmh.edu.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Saunders
authors.affiliation: Center 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. Electronic address: nmiller@cmh.edu.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Miller
authors.affiliation: 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. Electronic address: vsingh@cmh.edu.
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Singh
authors.affiliation: 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. Electronic address: dzwick@cmh.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Zwick
authors.affiliation: Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO 64108, USA. Electronic address: croberts@cmh.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Roberts
authors.affiliation: Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO 64108, USA; School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; Division of Hematology Oncology, Children's Mercy Hospital, Kansas City, MO 64108, USA. Electronic address: jddalal@cmh.edu.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Dalal
authors.affiliation: Center 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. Electronic address: sfkingsmore@cmh.edu.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
mesh_terms: D002648:Child; D059472:Exome; D005820:Genetic Testing; D014644:Genetic Variation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D025202:Molecular Diagnostic Techniques; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D053709:Interleukin-10 Receptor alpha Subunit
keywords: Colitis; Crohn's disease; Exome sequencing; Hematopoietic stem cell transplantation; IL10; IL10RA; Inflammatory bowel disease