Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: GTF3A

I don't know

Comment on list classification: There is one family reported with immunodeficiency and biallelic GTF3A variants, and functional evidenced available in support of the association. Hence, this gene can be rated amber with current evidence.

Created: 15 Aug 2025, 6:17 p.m. | Last Modified: 15 Aug 2025, 6:17 p.m.

Panel Version: 8.37

PMID:36399538 (2022) reported a non-consanguineous Belgian family in which the proband exhibited a common variable immunodeficiency (CVID) phenotype including susceptibility to bacterial upper respiratory infections, hypogammaglobulinemia, absent IgM and defective pneumococcal antibody responses requiring intravenous immunoglobulin replacement treatment. At the age of 9 months, the patient was hospitalized for HSE with positive HSV-1 PCR testing on cerebrospinal fluid and responded well to intravenous treatment with acyclovir.

The proband and his sister were identified with compound heterozygous variants in GTF3A gene (p.Cys195Trp and p.Cys219Arg). Proband's sister exhibited CVID-like adaptive immunological defects, some of which were notably different from the proband. She is HSV-1 seropositive and has no medical history of severe herpesviral infections, suggesting an autosomal recessive trait with incomplete penetrance for HSE.

There is functional evidence available from patient fibroblasts and GTF3A gene-edited cells, which displayed impaired HSV-1-induced innate immune responses and enhanced HSV-1 replication.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. It is rated Red in PanelApp Australia.

Created: 15 Aug 2025, 6:15 p.m. | Last Modified: 15 Aug 2025, 6:15 p.m.

Panel Version: 8.34

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
common variable immunodeficiency, MONDO:0015517

Publications

• 36399538

I don't know

PMID: 36399538 describe a case with CVID and HSV encephalitis with functional work. More cases are presented at ESID 2024 (unpublished yet).
Sources: Literature

Created: 17 Oct 2024, 9:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CVID with HSV encephalitis

Publications

• PMID: 36399538