Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: IRF4

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: As reviewed by Hannah Knight, there are two different heterozygous missense variants identified from seven unrelated cases reported with hypogammaglobulinemia/ combined immunodeficiency. In addition, there is supporting functional evidence for these variants. Hence, this gene can be promoted to green rating in the next GMS review.

Created: 30 Oct 2023, 5:14 p.m. | Last Modified: 30 Oct 2023, 5:14 p.m.

Panel Version: 4.59

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
combined immunodeficiency, MONDO:0015131

Green List (high evidence)

Two new papers reporting variants in this gene:
PMID: 36917008 - three patients from a multigeneration family with hypogammaglobulinemia - p.F359L
PMID: 36662884 - p.T95R in autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families

Created: 18 Oct 2023, 2:37 p.m. | Last Modified: 18 Oct 2023, 2:37 p.m.

Panel Version: 4.50

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Whipple's disease

Publications

• PMID: 36917008
• PMID: 36662884

Comment on list classification: Gene given Red gene status based on expert review. This gene is also found in the IUIS 2019 paper (PMID: 31953710)

Created: 22 Apr 2020, 12:06 p.m. | Last Modified: 22 Apr 2020, 12:06 p.m.

Panel Version: 2.110

Red List (low evidence)

Single family reported with Whipple's disease and a rare missense in IRF4. Younger healthy carrier members of the family had the same variant as older affected individuals, leading the authors to speculate about age-dependent penetrance. GWAS indicates separate link with skin/hair/eye pigmentation.
Sources: Expert list

Created: 16 Apr 2020, 11:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Whipple's disease; [Skin/hair/eye pigmentation, variation in, 8] 611724

Publications

• 29537367