Autoinflammatory Disorders
Gene: ARPC5
3 unrelated consanguineous families with homozygous variants and supporting in vitro functional assays. Immune dysregulation is a prominent feature of the condition. The IUIS IEI committee classify it as a disease of immune dysregulation in the subcategory of autoimmunity with or without lymphoproliferation.
Sources: Expert listCreated: 16 Nov 2024, 2:18 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency 133 with autoimmunity and autoinflammation MIM#620565
Publications
Variants in this GENE are reported as part of current diagnostic practice
Four individuals from 3 families reported. In addition to recurrent infections, features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis.
Sources: LiteratureCreated: 20 Nov 2023, 9:27 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565
Publications
4 individuals from 3 families reported with homozygous LoF variants. All had recurrent and severe infections. Other developmental anomalies were present but seemed variable.
PMID:37349293 reports 2 unrelated patients. Both had scoliosis. One had neurodevelopmental delay and brain atrophy. Patient 1 died at 15yo after a sudden episode of hemoptysis and hematochezia. Patient 2 died at 1yo because of progressive neurologic and respiratory disease; an autopsy was not performed.
PMID:37382373 reports 2 patients from the same family. One had multiple congenital anomalies including a congenital heart defect (CHD) (patent foramen ovale), cleft palate, and hypoplastic corpus callosum. The sibling also had CHD (moderate pulmonary stenosis and atrial septal defect).
Functional studies and a mouse model were supportive of the disease association.
Sources: LiteratureCreated: 6 Jul 2023, 2:56 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined immunodeficiency, ARPC5-related MONDO:0015131
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: arpc5 has been classified as Green List (High Evidence).
Gene: arpc5 has been classified as Green List (High Evidence).
gene: ARPC5 was added gene: ARPC5 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARPC5 were set to 37349293; 37382373 Phenotypes for gene: ARPC5 were set to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565 Review for gene: ARPC5 was set to GREEN