title: Novel exonic mutation inducing aberrant splicing in the IL10RA gene and resulting in infantile-onset inflammatory bowel disease: a case report.
abstract: BACKGROUND
  Although deleterious mutations in interleukin-10 and its receptor molecules cause severe infantile-onset inflammatory bowel disease, there are no reports of mutations affecting this signaling pathway in Japanese patients. Here we report a novel exonic mutation in the IL10RA gene that caused unique splicing aberrations in a Japanese patient with infantile-onset of inflammatory bowel disease in association with immune thrombocytopenic purpura and a transient clinical syndrome mimicking juvenile myelomonocytic leukemia.
  
  
  METHODS
  A Japanese boy, who was the first child of non-consanguineous healthy parents, developed bloody diarrhea, perianal fistula, and folliculitis in early infancy and was diagnosed with inflammatory bowel disease. He also developed immune thrombocytopenic purpura and transient features mimicking juvenile myelomonocytic leukemia. The patient failed to respond to various treatments, including elemental diet, salazosulfapyridine, metronidazole, corticosteroid, infliximab, and adalimumab. We identified a novel mutation (c.537G > A, p.T179T) in exon 4 of the IL10RA gene causing unique splicing aberrations and resulting in lack of signaling through the interleukin-10 receptor. At 21 months of age, the patient underwent allogeneic hematopoietic stem cell transplantation and achieved clinical remission.
  
  
  CONCLUSIONS
  We describe a novel exonic mutation in the IL10RA gene resulting in infantile-onset inflammatory bowel disease. This mutation might also be involved in his early-onset hematologic disorders. Physicians should be familiar with the clinical phenotype of IL-10 signaling defects in order to enable prompt diagnosis at an early age and referral for allogeneic hematopoietic stem cell transplantation.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. yanagi_tadahiro@med.kurume-u.ac.jp.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Yanagi
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. mizuochi_tatsuki@kurume-u.ac.jp.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Mizuochi
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. takaki_yuugo@med.kurume-u.ac.jp.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Takaki
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. eda_keisuke@med.kurume-u.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Eda
authors.affiliation: Division of Gastroenterology Department of Medicine, Kurume University School of Medicine, Kurume, Japan. ibd@med.kurume-u.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Mitsuyama
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ischii@pediatr.med.kyushu-u.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ishimura
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. takadah@pediatr.med.kyushu-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. dror.shouval@childrens.harvard.edu.|Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. dror.shouval@childrens.harvard.edu.
authors.forename: Dror S
authors.initials: DS
authors.lastname: Shouval
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. alexandra.griffith@childrens.harvard.edu.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Griffith
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. scott.snapper@childrens.harvard.edu.|Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. scott.snapper@childrens.harvard.edu.|Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA. scott.snapper@childrens.harvard.edu.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. yushiro@med.kurume-u.ac.jp.
authors.forename: Yushiro
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Medical Chemistry, Kurume University School of Medicine, Kurume, Japan. yamamoto_ken@med.kurume-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D005091:Exons; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000601:surgery; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D012074:Remission Induction / Q000379:methods
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10
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