Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: CBLB

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal 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
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: As reviewed by Boaz Palterer and reported in PMID:36006710, there are three unrelated cases and functional evidence are available for the association of biallelic CBLB variants with infantile-onset autoimmune disease (MIM #620430). Hence, this gene should be promoted to green rating in the next GMS review.

Created: 10 Jan 2024, 1:43 p.m. | Last Modified: 10 Jan 2024, 1:43 p.m.

Panel Version: 4.158

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autoimmune disease, multisystem, infantile-onset, 3, OMIM:620430

Publications

• 36006710

Red List (low evidence)

Janssen et al. described 3 unrelated children with early-onset autoimmunity with homozygous CBLB variants. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking.

Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient’s p.H285L mutation, had T and B cell hyperproliferation in response to antigen receptor cross-linking. CblbH257L mice had increased percentages of T regulatory cells (Tregs) that had normal in vitro suppressive function.
Sources: Literature

Created: 24 Oct 2023, 7:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
immunedysregulation; autoimmunity; hypothyroidism; diabetes mellitus type I; vitiligo; urticaria; HLH; ITP; autoimmune hemolytic anemia

Publications

• 36006710