Novel biallelic mutations in the DUOX2 gene underlying very early-onset inflammatory bowel disease: A case report

Reiko Kyodo, Ichiro Takeuchi, Satoshi Narumi, Hirotaka Shimizu, Kenichiro Hata, Takako Yoshioka, Kanako Tanase-Nakao, Toshiaki Shimizu, Katsuhiro Arai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Genetic variants affecting the function of dual oxidase 2 (DUOX2), the catalytic subunit of membrane-bound enzymes that produce hydrogen peroxide, are associated with very early-onset inflammatory bowel disease (VEO-IBD). We report the case of a 1-year-old boy diagnosed with VEO-IBD after presenting with bloody diarrhea. He had pancolitis and an extensive small intestinal ulcerative lesion at age 4 years. Infliximab treatment was successful but was discontinued due to delayed reaction. At age 7 years, treatment with ustekinumab was started, and remission has been maintained for more than 2 years. Whole-exome sequencing identified compound heterozygous missense DUOX2 variants of unknown significance (p.[R1212H];[F1490Y]). Protein expression in the whole-cell lysate and plasma membrane was lower in F1490Y-DUOX2 than in wild-type (WT)-DUOX2. Hydrogen peroxide generation upon ionomycin stimulation was lower in cells expressing R1212H-DUOX2 and F1490Y-DUOX2 than in those expressing WT-DUOX2. The novel, inherited, biallelic DUOX2 mutations may be molecular risk factors of VEO-IBD.

Original languageEnglish
Article number109015
JournalClinical Immunology
Volume238
DOIs
Publication statusPublished - 2022 May
Externally publishedYes

Keywords

  • Crohn's disease
  • Dual oxidase 2
  • Inflammatory bowel disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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