Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ARPC1B
A novel syndrome of combined immune deficiency, infections, allergy, and inflammation has been attributed to mutations in the gene encoding actin-related protein 2/3 complex subunit 1B (ARPC1B), which is a key molecule driving the dynamics of the cytoskeleton. Homozygous mutations in the ARPC1B gene have been found to result in the disruption of the protein structure and cause an autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation, increased levels of immunoglobulin E (IgE) and immunoglobulin A (IgA), and thrombocytopenia.Created: 9 Mar 2021, 8:41 a.m. | Last Modified: 9 Mar 2021, 8:41 a.m.
Panel Version: 2.402
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
combined immunodeficiency, infections, allergy, inflammation
Publications
Variants in this GENE are reported as part of current diagnostic practice
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
3 kindreds identified in 2 publications.Created: 19 Jun 2018, 5:17 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency with thrombocytopenia
Publications
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): ARPC1B .PanelApp HGNC gene symbol check: ARPC1B . IUIS Disease: ARPC1B deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal Numbers, .IUIS Other affected cells: N/A. IUIS Associated features: Mild thrombocytopenia with normal sized platelets, recurrent invasive infections, colitis, vasculitis, autoantibodies (ANA, ANCA), eosinophilia, defective Arp2/3, filament branching. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Immunodeficiency with Congenital ThrombocytopeniaCreated: 2 Jul 2018, 10:35 a.m.
Comment on publications: added third case PMID: 27965109Created: 20 Jun 2018, 2:50 p.m.
Comment on phenotypes: added phenotype suggested by external reviewCreated: 20 Jun 2018, 2:47 p.m.
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease associationCreated: 20 Jun 2018, 2:46 p.m.
Comment on publications: added publication suggested from external reviewCreated: 20 Jun 2018, 2:45 p.m.
After internal clinical review it was decided to leave as amber, whilst awaiting more information on this gene and potential disease association.Created: 11 May 2018, 3:32 p.m.
To be discussed with clinical team as to whether this is further demoted to Red. Two unrelated cases described but this is inflammatory predisposition not directly causative of itCreated: 11 May 2018, 11:45 a.m.
from OMIM: PLTEID is an autosomal recessive immune-mediated inflammatory disease with highly variable manifestations. More severely affected individuals have recurrent infections, vasculitis, and thrombocytopenia, whereas other patients have mild vasculitis and normal numbers of small platelets without severe infections. Laboratory studies show platelets with abnormal shape, decreased dense granules, and impaired spreading ability, as well as immune dysregulation with increased eosinophils, B cells, IgA and IgE, and autoantibodies (summary by Kahr et al., 2017)Created: 11 May 2018, 11:40 a.m.
Comment on phenotypes: inflammatory predisposition phenotype added.Created: 11 May 2018, 11:39 a.m.
Comment on publications: added publication to support association. PMID:28368018 Kahr et al. (2017) reported 3 patients from 2 unrelated families with a multisystem disorder characterized by platelet abnormalities, vasculitis, eosinophilia, and predisposition to inflammatory diseases.Created: 11 May 2018, 11:37 a.m.
Comment on phenotypes: added phenotype from OMIMCreated: 11 May 2018, 11:33 a.m.
Comment on mode of inheritance: added MOI from OMIMCreated: 11 May 2018, 11:33 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ARPC1B, GRID_Gene_Symbol: ARPC1B, GRID_Transcript_ENS_Community submitted: ENST00000252725, GRID_Transcript_RefSeq: NM_005720, GRID_Transcript_ENS_used_on_Production: ENST00000252725Created: 17 Apr 2018, 12:12 p.m.
Publications for gene: ARPC1B were set to 28368018; 29127144; 27965109
Phenotypes for gene: ARPC1B were changed from Thrombocytopenia & Immune Deficiency; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718; inflammatory predisposition; Immunodeficiency with thrombocytopenia; Mild thrombocytopenia with normal sized platelets, recurrent invasive infections, colitis, vasculitis, autoantibodies (ANA, ANCA), eosinophilia, defective Arp2/3, filament branching; Combined immunodeficiencies with associated or syndromic features to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718; Combined immune deficiency with or without thrombocytopenia; Inflammatory predisposition
Source NHS GMS was added to ARPC1B.
Source North West GLH was added to ARPC1B.
Source London North GLH was added to ARPC1B.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene ARPC1B were set to Thrombocytopenia & Immune Deficiency, Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718, inflammatory predisposition, Immunodeficiency with thrombocytopenia, Mild thrombocytopenia with normal sized platelets, recurrent invasive infections, colitis, vasculitis, autoantibodies (ANA, ANCA), eosinophilia, defective Arp2/3, filament branching, Combined immunodeficiencies with associated or syndromic features
IUIS Classification February 2018 was added to ARPC1B. Panel: Primary immunodeficiency disorders
Gene: arpc1b has been classified as Green List (High Evidence).
Publications for gene: ARPC1B were set to 28368018; 29127144; 27965109
Phenotypes for gene: ARPC1B were set to Thrombocytopenia & Immune Deficiency; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718; inflammatory predisposition; Immunodeficiency with thrombocytopenia
Gene: arpc1b has been classified as Green List (High Evidence).
Publications for gene: ARPC1B were set to 28368018; 29127144
Phenotypes for ARPC1B were set to Thrombocytopenia & Immune Deficiency; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718; inflammatory predisposition
Publications for ARPC1B were set to 28368018
Phenotypes for ARPC1B were set to Thrombocytopenia & Immune Deficiency; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718
Mode of inheritance for ARPC1B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Expert Review Amber was added to ARPC1B. Panel: Primary immunodeficiency disorders
Phenotypes for gene ARPC1B were set to Thrombocytopenia & Immune Deficiency
ARPC1B was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
ARPC1B was created by Louise Daugherty