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

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. •Novel heterozygous DUOX2 mutations in very-early-onset inflammatory bowel disease•The functional analysis revealed the mutations led to decreased H2O2 production•The first case of IBD with DUOX2 mutation that achieved remission with ustekinumab•The findings of endoscopy before and after ustekinumab are shown in Figure•The previously reported cases with IBD with DUOX2 mutations are summarized in Table