Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: IRF4
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
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 familiesCreated: 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
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
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 listCreated: 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
Tag Q4_23_promote_green tag was added to gene: IRF4. Tag Q4_23_NHS_review tag was added to gene: IRF4.
Phenotypes for gene: IRF4 were changed from Whipple's disease; [Skin/hair/eye pigmentation, variation in, 8] 611724 to combined immunodeficiency, MONDO:0015131
Publications for gene: IRF4 were set to 29537367; 31953710
Gene: irf4 has been classified as Amber List (Moderate Evidence).
Publications for gene: IRF4 were set to 29537367
Gene: irf4 has been classified as Red List (Low Evidence).
gene: IRF4 was added gene: IRF4 was added to Primary immunodeficiency. Sources: Expert list Mode of inheritance for gene: IRF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IRF4 were set to 29537367 Phenotypes for gene: IRF4 were set to Whipple's disease; [Skin/hair/eye pigmentation, variation in, 8] 611724 Review for gene: IRF4 was set to RED