Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ZNFX1
15 individuals from 8 families reported with multi-system inflammation and susceptibility to viral infections.
In addition, four indviduals from two unrelated kindreds reported with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis.Created: 10 May 2021, 10:33 a.m. | Last Modified: 10 May 2021, 10:33 a.m.
Panel Version: 2.421
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Multisystem inflammation; susceptibility to viral infections
Publications
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: New gene added by Boaz Palterer. Sufficient number of unrelated cases (10 - PMIDs: 33876776; 33872655) with immunopathology and biallelic variants in this gene to rate as Green at the next GMS panel update.Created: 27 Apr 2021, 10:43 a.m. | Last Modified: 27 Apr 2021, 10:43 a.m.
Panel Version: 2.416
- Voyer et al. 2021 (PMID: 33876776) - Three patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette–Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. Both families were homozygous for different pLoF ZNFX1 variants (c.2876C>G, p.S959* and c.4815_4818del, p.E1606Rfs*10, respectively).
- Vavassori et al. 2021 (PMID: 33872655) - 13 patients from 8 families with immunodeficiency characterised by severe viral infections and systemic inflammatory disease, associated with biallelic variants in the ZNFX1 gene. Studies using patient-derived primary cells showed deregulated expression of interferon-stimulated genes and impaired clearance of virus infections by monocytes.Created: 27 Apr 2021, 10:39 a.m. | Last Modified: 27 Apr 2021, 10:39 a.m.
Panel Version: 2.414
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Multisystem Inflammation and Susceptibility to Viral infections in Human ZNFX1 Deficiency
15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic-lymphohistiocytosis-like disease, early-onset seizures, as well as renal and lung disease.
https://www.jacionline.org/article/S0091-6749(21)00613-8/fulltextCreated: 20 Apr 2021, 7:51 a.m. | Last Modified: 20 Apr 2021, 7:51 a.m.
Panel Version: 2.413
Le Voyer et al. described two patients from two unrelated kindreds with homozygous LOF variants in the ZNFX1 gene associated with mendelian susceptibility to mycobacterial disease (MSMD) and monocytosis. ( https://www.pnas.org/content/118/15/e2102804118 )
Sources: LiteratureCreated: 10 Apr 2021, 7:13 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Multisystem inflammatory disoder; viral infections; HLH
Tag gene-checked tag was added to gene: ZNFX1.
Tag Q2_21_rating was removed from gene: ZNFX1.
Source Expert Review Green was added to ZNFX1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: znfx1 has been classified as Amber List (Moderate Evidence).
Publications for gene: ZNFX1 were set to
Tag Q2_21_rating tag was added to gene: ZNFX1.
gene: ZNFX1 was added gene: ZNFX1 was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ZNFX1 were set to mendelian susceptibility to mycobacterial disease; MSMD; monocytosis. Penetrance for gene: ZNFX1 were set to unknown Review for gene: ZNFX1 was set to RED