Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: IKZF3
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:59 a.m. | Last Modified: 8 Mar 2022, 10:59 a.m.
Panel Version: 2.532
Comment on list classification: Upgraded from Red to Amber but there is now enough evidence to promote this gene to Green at the next GMS panel update. Two unrelated families displaying comparable immunologic disorders including T and B cell abnormalities with recurrent infections (PMID: 34155405; 34694366). Strong functional support including animal model and in vitro studies.Created: 15 Nov 2021, 12:17 p.m. | Last Modified: 15 Nov 2021, 12:20 p.m.
Panel Version: 2.493
Comment on mode of pathogenicity: Variants discovered to date located in DNA binding domain of IKZF3/AIOLOS, with dominant-negative effect on WT.Created: 15 Nov 2021, 12:17 p.m. | Last Modified: 15 Nov 2021, 12:17 p.m.
Panel Version: 2.491
Comment on list classification: New gene added by Boaz Palterer (University of Florence). Rating Red as only a single family with B cell deficiency has been reported at this time. Includes supportive mouse model showing B cell developmental defects and T cell abnormalities (PMID:34155405).Created: 29 Jun 2021, 9:22 a.m. | Last Modified: 29 Jun 2021, 9:22 a.m.
Panel Version: 2.435
New kindred with 4 affected subjects reported with autosomal dominant IKZF3 variant ( p.N160S ) by Kuehn et al.Created: 27 Oct 2021, 10:30 a.m. | Last Modified: 27 Oct 2021, 10:30 a.m.
Panel Version: 2.480
Motoi Yamashita et al. ( https://www.nature.com/articles/s41590-021-00951-z ) identified 3 patients from a kindred harboring the missense G159R variant in AIOLOS, encoded by the IKZF3 gene. They demonstrated that the variant acts as a dominant-negative mutation through heterodimeric interference by disrupting IKAROS (IKZF1) function.
Sources: LiteratureCreated: 22 Jun 2021, 10:43 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
B cell deficiency; EBV inefctions suspectibility; hypogammaglobulinemia; T and B cell abnormalities; pneumocystis pneumonia; chronic lymphocytic leukemia
Publications
Tag Q4_21_rating was removed from gene: IKZF3.
Source Expert Review Green was added to IKZF3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: ikzf3 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: IKZF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene: IKZF3 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: IKZF3 were set to 34155405
Tag Q4_21_rating tag was added to gene: IKZF3.
Phenotypes for gene: IKZF3 were changed from B cell deficiency; EBV inefctions suspectibility; hypogammaglobulinemia to Immunodeficiency 84, OMIM:619437
Publications for gene: IKZF3 were set to
Gene: ikzf3 has been classified as Red List (Low Evidence).
gene: IKZF3 was added gene: IKZF3 was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: IKZF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: IKZF3 were set to B cell deficiency; EBV inefctions suspectibility; hypogammaglobulinemia Penetrance for gene: IKZF3 were set to unknown Review for gene: IKZF3 was set to RED