Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: AICDA
Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update.Created: 5 Jan 2024, 12:02 p.m. | Last Modified: 5 Jan 2024, 12:02 p.m.
Panel Version: 4.151
IUIS (June 2022) includes both AD and AR forms of AID deficiency. On this basis, the MOI should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update.
IUIS (PMID: 35748970): AR (Low IgG and IgA with normal or high IgM. Associated with bacterial infections, enlarged lymph nodes and germinal centers). AD (Low IgG and IgA with normal or high IgM. Normal B cell count. Associated with bacterial infections, enlarged lymph nodes and germinal centers).
Review of published case reports revealed hyper-IgM syndrome associated with the same heterozygous variant c.568C>T (p.R190X) in 8 Japanese patients from four unrelated families (PMID: 14564357; 15893695), 5 individuals from one European family (4 generations), plus an additional unrelated individual of unspecified descent (PMID: 35271747).
In vitro studies confirmed that the p.R190X variant leads to impaired class switching in CD138++ plasma cells, resulting in hyposecretion of IgG with normal production of IgM.Created: 5 Jan 2024, 12:01 p.m. | Last Modified: 5 Jan 2024, 12:01 p.m.
Panel Version: 4.149
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency with hyper-IgM, type 2, OMIM:605258
Publications
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
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): AICDA .PanelApp HGNC gene symbol check: AICDA . IUIS Disease: AID deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Bacterial infections, enlarged lymph nodes and germinal centers. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in Serum IgG and IgA with Normal/Elevated IgM and Normal Numbers of B cells, Hyper IgMCreated: 2 Jul 2018, 10:35 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: AID, PanelApp HGNC gene symbol check: AICDA, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Class switch recombination defects (CSR) / HIGM syndromes / CSR defects and Hyper IgM (HIGM) syndromesCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: AICDA, GRID_Gene_Symbol: AICDA, GRID_Transcript_ENS_Community submitted: ENST00000229335, GRID_Transcript_RefSeq: NM_020661.2, GRID_Transcript_ENS_used_on_Production: ENST00000229335Created: 17 Apr 2018, 12:12 p.m.
Comment on list classification: After searching the four sources (UKGTN, Illumina, Radboud and Emory), we have decided that there is a high level of evidence for this gene.Created: 15 Aug 2017, 12:29 p.m.
Mode of inheritance for gene: AICDA was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AICDA were set to 12958596; 21700883; 27701145
Tag recurrent-variant tag was added to gene: AICDA. Tag Q4_23_MOI tag was added to gene: AICDA.
Phenotypes for gene: AICDA were changed from Immunodeficiency with hyper-IgM, type 2; Hyper IgM syndrome with lymphoid hyperplasia; Immunodeficiency with hyper-IgM, type 2, 605258; Primary Immune Deficiencies; CSR defects and Hyper IgM (HIGM) syndromes; Bacterial infections, enlarged lymph nodes and germinal centers; Predominantly Antibody Deficiencies to Immunodeficiency with hyper-IgM, type 2, OMIM:605258
Source NHS GMS was added to AICDA.
Source North West GLH was added to AICDA.
Source London North GLH was added to AICDA.
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 AICDA were set to Immunodeficiency with hyper-IgM, type 2, Hyper IgM syndrome with lymphoid hyperplasia, Immunodeficiency with hyper-IgM, type 2, 605258, Primary Immune Deficiencies, CSR defects and Hyper IgM (HIGM) syndromes, Bacterial infections, enlarged lymph nodes and germinal centers, Predominantly Antibody Deficiencies
IUIS Classification February 2018 was added to AICDA. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to AICDA. Panel: Primary immunodeficiency disorders
Gene: aicda has been classified as Green List (High Evidence).
ESID Registry 20171117 was added to AICDA. Panel: Primary immunodeficiency disorders Phenotypes for gene AICDA were set to Immunodeficiency with hyper-IgM, type 2, Hyper IgM syndrome with lymphoid hyperplasia, Immunodeficiency with hyper-IgM, type 2, 605258, Primary Immune Deficiencies, CSR defects and Hyper IgM (HIGM) syndromes
Phenotypes for gene AICDA were set to Immunodeficiency with hyper-IgM, type 2, Hyper IgM syndrome with lymphoid hyperplasia, Immunodeficiency with hyper-IgM, type 2, 605258, Primary Immune Deficiencies
GRID V2.0 was added to AICDA. Panel: Primary immunodeficiency disorders Phenotypes for gene AICDA were set to Immunodeficiency with hyper-IgM, type 2, Hyper IgM syndrome with lymphoid hyperplasia, Immunodeficiency with hyper-IgM, type 2, 605258, Primary Immune Deficiencies
GOSH PID v.8.0 was added to AICDA. Panel: Primary immunodeficiency disorders
AICDA Source: GOSH PID 20171130 was removed from gene: AICDA
GOSH PID 20171130 was added to AICDA. Panel: Primary immunodeficiency disorders
AICDA was added to Primary immunodeficiency disorders panel. Sources: Expert Review Green, A- or hypo-gammaglobulinaemia v1.25
AICDA was created by Louise Daugherty