Combined Immunodeficiency

Gene: ARPC5

Green List (high evidence)

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.

Created: 20 Nov 2023, 9:25 a.m. | Last Modified: 20 Nov 2023, 9:25 a.m.

Panel Version: 1.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565

Green List (high evidence)

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: Literature

Created: 6 Jul 2023, 2:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined immunodeficiency, ARPC5-related MONDO:0015131

Publications

• 37349293
• 37382373

Variants in this GENE are reported as part of current diagnostic practice