Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ARPC5

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There are at least three unrelated cases and supporting functional evidence available for the association of this gene with immunodeficiency. Hence, this gene can be promoted to green rating in the next GMS review.

Created: 30 Aug 2023, 11:54 a.m. | Last Modified: 30 Aug 2023, 11:54 a.m.

Panel Version: 4.26

PMID:37349293 - Two unrelated patients were identified with biallelic null variants in ARPC5 gene and presented with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms.

PMID:37382373 - A female child was identified with biallelic ARPC5 frameshift variants and presented with recurrent infections, multiple congenital anomalies, diarrhea and thrombocytopenia, and suffered early demise from sepsis. Her parents also had a previous child who died with similar clinical features.

In addition, there are functional studies and mouse model available in support of this gene-disease association.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.

Created: 30 Aug 2023, 11:51 a.m. | Last Modified: 30 Aug 2023, 11:51 a.m.

Panel Version: 4.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
combined immunodeficiency, MONDO:0015131

Publications

• 37349293
• 37382373

Green List (high evidence)

Nunes-Santos et al. described 2 unrelated patients from 2 kindreds woith germline biallelic null mutations in ARPC5 presenting with a complex actinopathy phenotype of increased susceptibility to infections, autoimmunity, inflammation, and dysmorphisms.
There is strong biological rationale: ARPC5 is part of the Arp2/3 complex, related to WAS in Wiskott-Aldrich syndrome and ARPC1B deficiency. Strong functional ex vivo and in vitro data is presented.
( https://doi.org/10.1038/s41467-023-39272-0 )
Sources: Literature

Created: 22 Jun 2023, 4:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
immunodeficiency; autoimmunity; inflammation; dysmorphisms; impaired wound healing; scoliosis; pneumatoceles; anemia