Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RHBDF2

Comment on list classification: New gene added by Boaz Palterer. Not yet associated with an immune phenotype in OMIM or G2P, but note that monoallelic variants in this gene are associated with tylosis.

To date, 4 individuals from 2 unrelated families have been reported (PMID: 34937930) with LoF variants in this gene and recurrent infections. Functional data includes supportive mouse model.

Rating Amber for now awaiting at least one more corroborating case (added watchlist tag)

Created: 11 May 2023, 4:28 p.m. | Last Modified: 11 May 2023, 4:28 p.m.

Panel Version: 4.9

Red List (low evidence)

iRHOM deficiency with Respiratory and Intestinal inflammation and cytokine Secretion defect’ (IRIS): Kubo et al. (https://www.nature.com/articles/s41590-021-01093-y) described a new immunodeficiency disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in 4 subjects across two kindreds with recurrent infections in different organs. The disease presentation is pleiotropic, with one patient with recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement and the other two experienced recurrent respiratory infections. They replicated the phenotype in a KO mouse model and provided functional data.
Sources: Literature

Created: 23 Dec 2021, 9:18 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pneumonia; Colitis; Immunodeficiency