Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: DUOX2

Green List (high evidence)

MONOALLELIC CASES:
PMID: 26301257 Hayes et al., 2015
2 male probands, diagnosed with IBD / ulcerative colitis at 4.7 and 4.3 yrs. Het for DUOX2 missense variants.

Adding watchlist_moi tag to monitor for heterozygous case reports.

Created: 29 Jul 2026, 3 p.m. | Last Modified: 29 Jul 2026, 3 p.m.

Panel Version: 9.37

Comment on list classification: As reviewed by Boaz Palterer, there are more than 3 unrelated individuals reported in literature with biallelic DUOX2 variants and very early-onset inflammatory bowel disease. Hence, this gene can be promoted to Green at the next update.

Created: 29 Jul 2026, 2:38 p.m. | Last Modified: 29 Jul 2026, 2:38 p.m.

Panel Version: 9.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
inflammatory bowel disease; MONDO:0005265

Publications

• 26301257
• 28683258
• 35429653
• 38075699

Green List (high evidence)

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: 17 Jun 2026, 2:48 p.m.

Mode of inheritance
Unknown

Phenotypes
Inflammatory bowel disease; IBD; VEOIBD

Publications

• 38075699
• 26301257
• 35429653