Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: FNIP1

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.

Panel Version: 2.529

Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 5 unrelated cases with immunodeficiency associated with biallelic FNIP1 variants, as well as supportive functional data and animal model.

Created: 18 Sep 2020, 12:02 p.m. | Last Modified: 18 Sep 2020, 12:02 p.m.

Panel Version: 2.191

- PMID: 32181500 (2020) - Three patients from two independent consanguineous families with homozygous variants (c.3353G>A, p.Ser1118Asn and c.1289delA, p.His430Profs7*) in the FNIP1 gene. Both variants segregated with the disease phenotype in each family. Clinically, patients presented with combined immunodeficiency, cardiac findings (hypertrophic cardiomyopathy, Wolff‐Parkinson‐White syndrome), and myopathy of skeletal muscles with motor DD. Authors note phenotypic overlap with the murine model of FNIP1 deficiency, but no functional analyses of the variants or patient cells were performed.

- PMID: 32905580 (2020) - Three cases from unrelated families, all harbouring novel biallelic variants in FNIP1. Clinical manifestations in all patients include hypertrophic cardiomyopathy, severe and/or recurrent infections, absent circulating B-cells, and agammaglobulinemia; as well as either severe or intermittent neutropenia in two cases. Functional studies showed impairment of B-cell metabolism, including disruptions to mitochondrial numbers/activity and the PI3K/AKT pathway.

Created: 18 Sep 2020, 11:58 a.m. | Last Modified: 18 Sep 2020, 11:58 a.m.

Panel Version: 2.190

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 32181500
• 32905580

I don't know

Sources: Literature

Created: 11 Sep 2020, 3 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary Immunodeficiency; Agammaglobulinemia; Hypertrophic Cardiomyopathy; Neutropenia

Publications

• 32905580