Cardiomyopathies - including childhood onsetGene: FNIP1
Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 5 unrelated cases with hypertrophic cardiomyopathy associated with biallelic FNIP1 variants, as well as supportive functional data and animal model.
Created: 18 Sep 2020, 1:19 p.m. | Last Modified: 18 Sep 2020, 1:19 p.m.
Panel Version: 1.9
- 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, 1:17 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia
Tag for-review tag was added to gene: FNIP1.
Gene: fnip1 has been classified as Amber List (Moderate Evidence).
gene: FNIP1 was added gene: FNIP1 was added to Cardiomyopathies - including childhood onset. Sources: Literature Mode of inheritance for gene: FNIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FNIP1 were set to 32181500; 32905580 Phenotypes for gene: FNIP1 were set to Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia Review for gene: FNIP1 was set to GREEN