Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: IVNS1ABP
Comment on list classification: Rating Amber in view of the possibility of incomplete penetrance, and uninformative segregation analysis in 2/3 cases. Awaiting additional publications/clinical evidence to validate association (added to watchlist).Created: 11 Aug 2020, 2:20 p.m. | Last Modified: 11 Aug 2020, 2:20 p.m.
Panel Version: 2.184
PMID: 32499645 (2020) - Three unrelated families with LOF variants (1 intragenic deletion, 2 distinct nonsense variants) in the IVNS1ABP gene. All affected patients presented with an immunologic disorder characterised by severe recurrent cutaneous warts on the hands, feet, and face. Additional variable features of immunodeficiency and autoinflammation included recurrent infections, colitis, and retinal vasculitis. Laboratory studies showed that all variant carriers exhibited low CD4+ T cells and numbers of total T cells and B cells towards the lower limit of the normal range. Western blot analysis showed a ~50% reduction of IVNS1ABP protein in patient peripheral blood cells compared to control individuals, consistent with haploinsuffiency.
In kindred A, the mother of the proband also carried the variants - she did show a low CD4+ T cell and CD19+ B cell count; however, she did not have a history of infection. Therefore, the possibility of incomplete penetrance should be considered. In kindred B, the variant was not present in the unaffected father or brother; the mother was not available for genetic investigation. In kindred C, neither parent was available for investigation.Created: 10 Aug 2020, 2:27 p.m. | Last Modified: 10 Aug 2020, 2:27 p.m.
Panel Version: 2.175
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Immunodeficiency 70, 618969
Publications
3 unrelated families with putative loss of function variants. Case features and immunophenotyping of patient cells is suggestive of a combined immune deficiency, based on the ESID definitions of PID subtypes.Created: 3 Aug 2020, 11:04 a.m. | Last Modified: 3 Aug 2020, 11:04 a.m.
Panel Version: 2.175
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Immunodeficiency 70, MIM#618969
Publications
Variants in this GENE are reported as part of current diagnostic practice
One of the 25 top novel PID-associated genes in a large-cohort WGS analysis, using BeviMed assessment of enrichment for candidate disease-causing variants in individual genes (https://doi.org/10.1101/499988).Created: 26 May 2020, 8:36 a.m. | Last Modified: 26 May 2020, 8:36 a.m.
Panel Version: 2.175
Mode of inheritance
Unknown
Phenotypes
primary immunodeficiency
Publications
Tag watchlist tag was added to gene: IVNS1ABP.
Gene: ivns1abp has been classified as Amber List (Moderate Evidence).
Tag for-review was removed from gene: IVNS1ABP.
Tag for-review tag was added to gene: IVNS1ABP.
Phenotypes for gene: IVNS1ABP were changed from primary immunodeficiency to Immunodeficiency 70, MIM#618969
Publications for gene: IVNS1ABP were set to
Mode of inheritance for gene: IVNS1ABP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: ivns1abp has been classified as Amber List (Moderate Evidence).
gene: IVNS1ABP was added gene: IVNS1ABP was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: IVNS1ABP was set to Unknown Phenotypes for gene: IVNS1ABP were set to primary immunodeficiency