Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: AIRE

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.

Created: 14 Oct 2020, 12:23 p.m. | Last Modified: 14 Oct 2020, 12:23 p.m.

Panel Version: 2.220

The following PubMed IDs were added to entity AIRE: 29483906;9735375;28257655;30565240;29949487. These publications have been associated with OMIM phenotype MIM#240300, which is listed for this entity, by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Publications

• 29483906
• 9735375
• 28257655
• 30565240
• 29949487

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Green List (high evidence)

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): AIRE .PanelApp HGNC gene symbol check: AIRE . IUIS Disease: APECED (APS-1), autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy . IUIS Inheritance: AR or AD .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Autoimmunity: hypoparathyroidism hypothyroidism, adrenal insufficiency, diabetes, gonadal dysfunction and other endocrine abnormalities, chronic mucocutaneous candidiasis, dental enamel hypoplasia, alopecia areata enteropathy, pernicious anemia. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Autoimmunity with or without Lymphoproliferation

Created: 2 Jul 2018, 10:35 a.m.

Comment on mode of inheritance: updated MOI from external expert review

Created: 13 Jun 2018, 1:43 p.m.

Comment on list classification: Changed from Amber to Green there are more than 3 unrelated cases to support the PID phenotype.

Created: 1 May 2018, 11:54 a.m.

Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype. Recent papers PMID: 28911151 (2017)- largest cohort (112) of patients with clinically characterized APS-1 to date and PMID: 29108822 (2018)

Created: 1 May 2018, 11:50 a.m.

Comment on publications: added publications to support PID phenotype

Created: 1 May 2018, 11:39 a.m.

Comment on mode of inheritance: Changed MOI from AR to both since there is some evidence for monoallelic inheritance PMID: 11600535 (2001) identified an Italian family with autoimmune polyendocrinopathy syndrome and a pattern of inheritance suggestive of a dominant mechanism.

Created: 1 May 2018, 11:23 a.m.

from Orphanet: Autoimmune polyendocrinopathy type 1, or APECED syndrome, is a genetic disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.

Created: 1 May 2018, 11:18 a.m.

Comment on phenotypes: added OMIM MIMid and synonyms

Created: 1 May 2018, 11:12 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 downloaded from ESID Registry. ESID_Gene_original: AIRE, PanelApp HGNC gene symbol check: AIRE, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Chronic mucocutaneous candidiasis (CMC) / Chronic mucocutaneous candidiasis (CMC); Diseases of immune dysregulation / Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) / Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: AIRE, GRID_Gene_Symbol: AIRE, GRID_Transcript_ENS_Community submitted: ENST00000291582, GRID_Transcript_RefSeq: NM_000383.3, GRID_Transcript_ENS_used_on_Production: ENST00000291582

Created: 17 Apr 2018, 12:12 p.m.