Predominantly Antibody Deficiency

Gene: FNIP1

Green List (high evidence)

PMID: 37522988 (2023)- Additional patient with - Peripheral B cell deficiency, severe hypogammaglobulinemia/agammaglobulinemia, intermittent neutropenia responsive to G-CSF treatment, in conjunction with hypertrophic cardiomyopathy of the ventricle associated with Wolff-Parkinson-White Syndrome, and psycho-motor as well as intellectual developmental delay.

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.
Sources: Literature

Created: 11 Aug 2023, 1:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia; Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705

Publications

• PMID: 37522988
• PMID: 32181500
• PMID: 32905580 (2020)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705

Green List (high evidence)

- 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.
Sources: Literature

Created: 18 Sep 2020, 2:13 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia

Publications

• 32181500
• 32905580