Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ARPC5
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
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: LiteratureCreated: 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
Tag Q3_23_promote_green tag was added to gene: ARPC5.
Gene: arpc5 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ARPC5 were changed from immunodeficiency; autoimmunity; inflammation; dysmorphisms; impaired wound healing; scoliosis; pneumatoceles; anemia to combined immunodeficiency, MONDO:0015131
Publications for gene: ARPC5 were set to
gene: ARPC5 was added gene: ARPC5 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARPC5 were set to immunodeficiency; autoimmunity; inflammation; dysmorphisms; impaired wound healing; scoliosis; pneumatoceles; anemia Penetrance for gene: ARPC5 were set to unknown Review for gene: ARPC5 was set to GREEN