Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: LY96

Red List (low evidence)

Li et al. described 2 patients from 1 kindred, harboring a homozygous mutation in the LY96 gene (c.347_349delCAA). They presented with very early-onset inflammatory bowel disease, recurrent pneumonia, and otitis media. The underlying mechanism and phenotype were validated in vitro using genetically engineered induced pluripotent stem cell (iPSC)-derived macrophages. Both LY96 knockout models and the specific patient mutation knock-in models successfully recreated the immunodeficiency phenotype, demonstrating impaired activation of NF-κB and MAPK signaling, defective TLR4 endocytosis, and significantly decreased cytokine expression (e.g., IL-6, TNF, IL-10) upon challenge with lipopolysaccharide (LPS) and Gram-negative bacteria, while host defense responses to Gram-positive bacteria remained intact.
Sources: Expert list, Literature

Created: 17 Jun 2026, 4:25 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Inflammatory bowel disease; Pneumonia; Otitis media; Abnormal inflammatory response; Recurrent bacterial infections

Publications

• 36462957