Intestinal failure or congenital diarrhoea

Gene: DUOX2

Red List (low evidence)

Comment on list classification: There are more than 3 unrelated individuals reported in literature with biallelic DUOX2 variants and very early onset IBD, including bloody diarrhea. However, these cases do not meet the Test Directory criterion of neonatal onset (first 28 days of life). Hence, the gene should remain Red on this panel.

Created: 29 Jul 2026, 2:55 p.m. | Last Modified: 29 Jul 2026, 2:55 p.m.

Panel Version: 3.16

PMID: 26301257 - 2 male probands, diagnosed with IBD / ulcerative colitis at 4.7 and 4.3 yrs. Het for DUOX2 missense variants.
PMID: 28683258 - Male proband comp het for NM_014080.4:c.1825G>A; p.P609S and NM_014080.4:c.857G>A; R286H in DUOX2. He developed pancolitis with bloody diarrhea at the age of 3.
PMID: 35429653 - report 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.
PMID: 38075699 - Female proband diagnosed with IBD at 1 month. The infant was asymptomatic with no intestinal symptoms such as abdominal pain, rectal bleeding, perianal disease, diarrhea, or intestinal obstruction. The only sign of intestinal involvement was increased inflammatory markers.

Created: 29 Jul 2026, 2:53 p.m. | Last Modified: 29 Jul 2026, 2:53 p.m.

Panel Version: 3.15

Literature review by Boaz Palterer (University of Florence), copied from Primary immunodeficiency or monogenic inflammatory bowel disease:
DUOX2 encodes Dual Oxidase 2, an H2O2-producing NADPH oxidase primarily expressed at the apical membranes of enterocytes, where it plays a critical role in maintaining intestinal microbial homeostasis and innate immune defense. While biallelic variants in DUOX2 are classically associated with congenital hypothyroidism (Thyroid dyshormonogenesis 6; OMIM 607200), a distinct phenotype linking DUOX2 deficiency to Inborn Errors of Immunity (IEI) and very early-onset inflammatory bowel disease (VEO-IBD) has been reported in several case reports.

The initial association was reported when inactivating missense variants in DUOX2 were identified in VEO-IBD patients, resulting in significantly reduced reactive oxygen species (ROS) production by intestinal epithelial cells and defective host resistance to enteric pathogens like Campylobacter jejuni (Hayes et al., 2015). More recently, the phenotypic spectrum has been expanded to include monogenic neonatal-onset IBD. Patients with compound heterozygous DUOX2 variants have presented with severe intestinal inflammation and colon stenosis shortly after birth, displaying significantly decreased catalytic activity without concurrent clinical hypothyroidism (Finocchi et al, Kyodo et al. Crawford et al. ).

Hayes described 2 patient with heterozgous DUOX2 VUS and VEOIBD
https://pmc.ncbi.nlm.nih.gov/articles/PMC4539615/

Finocchi et al described 1 month old with VEOIBD with compound heterozygous VUS in DUOX2
https://pubmed.ncbi.nlm.nih.gov/38075699/

Kyodo et al. described 1 year old with VEOIBD with compound heterozygous VUS in DUOX2
https://pubmed.ncbi.nlm.nih.gov/35429653/

Crawford et al, additional case report: 5-year-old male with compound heterozygous VUS in DUOX2
https://rupress.org/jhi/article/1/CIS2025/CIS2025abstract.49/277486/Biallelic-DUOX2-Variants-and-the-Link-to-Very
Sources: Literature

Created: 29 Jul 2026, 2:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
inflammatory bowel disease, MONDO:0005265

Publications

• 26301257
• 28683258
• 35429653
• 38075699