Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: IRAK2

I don't know

12 patients from 11 unrelated, non-consanguineous Chinese families, homozygous c.95_277del (p.Ala32_Trp93delinsGly, exon 2 deletion, IRAK2-delta-ex2), causing immune dysregulation: recurrent infections, autoimmunity (4 with SLE and lupus nephritis) and autoinflammation. Disease status segregated strictly with biallelic inheritance in all 11 pedigrees; 11 of 12 clinically affected, 1 preclinical (possible reduced penetrance); onset from 1 month to adulthood. Myddosome assembly disrupted (loss of IRAK4 interaction), confirmed functionally with knock-in mouse and rescue. PMID 42168171. Note: the 2 patients of PMID 39299377 are not counted - the primary study tested both variants (p.L78P, p.R506W) and classified them as benign, so independent confirmation is not yet established.

Created: 6 Oct 2026, 6:07 p.m. | Last Modified: 6 Oct 2026, 6:07 p.m.

Panel Version: 9.109

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 39299377
• 42168171