COVID-19 researchGene: CD8A
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CD8A .PanelApp HGNC gene symbol check: CD8A . IUIS Disease: CD8 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections, may be asymptomatic. IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined Immunodeficiency
Created: 2 Jul 2018, 10:35 a.m.
Keep amber after external expert review until more info on gene and disease association
Created: 27 Jun 2018, 7:13 p.m.
Kept Amber to Green after internal clinical review, it was noted that there is a single variant in a single population without any functional work up to support this variant or the mechanism. Feeding back all rare variants in this gene currently would not seem to beneficial, in particular when the Immunologists would be able to identify isolated CD8+ lymphocyte deficiency through their work up (T cell subset testing). Keep Amber until further evidence on gene/variants.
Created: 15 Jun 2018, 9:50 a.m.
Past onto clinical team for further discussion. Our current PanelApp rules denote that for a founder mutation we cannot make these genes Green. There are exceptions to this rule (reviewed by clinical team) if there has been an additional pathogenic var. conformed/reported. In this instance there is currently only one mutation that gives rise to observed PID phenotype.
Created: 11 Jun 2018, 2:19 p.m.
added founder -effect tag
Created: 11 Jun 2018, noon
Comment on publications: de la Calle-Martin et al. (2001) PMID: 11435463 described a patient of Spanish-gyypsy origin with recurrent bacterial and viral infections and total absence of CD8-positive T cells, and identified a homozygous 331G-A transition in the CD8A gene, resulting in a gly90-to-ser (G90S) substitution in a conserved residue in the immunoglobulin domain of the protein.
Mancebo E et al. (2008) PMID:17658607 describes the second case for CD8 immunodeficiency confirming the pathogenic effect of p.Gly111Ser, the same variant as previously reported by de la Calle-Martin et al. (2001). Looking at 1127 unrelated control individuals: 734 subjects of Gypsy ancestry from different sub-isolates and geographic locations in Europe, and 393 of Spanish (non-Gypsy) ethnicity. The result indicated that p.Gly111Ser is confined to the Spanish Gypsy population, where it occurs at a carrier rate of 0.4%. Analysis of microsatellite markers flanking the CD8A mutated gene revealed a shared polymorphic haplotype suggesting a common founder for p.Gly111Ser mutation that causes CD8 deficiency in the Spanish Gypsy population. CD8 immunodeficiency should be given diagnostic consideration in Spanish Gypsies with recurrent infections.
Created: 11 Jun 2018, 11:49 a.m.
Comment on phenotypes: added phenotype from Orphanet and OMIN MIMid. Susceptibility to respiratory infections associated with CD8 alpha chain mutation is a rare primary immunodeficiency due to a defect in adaptive immunity characterized by the absence of CD8+ T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity range from fatal respiratory insufficiency to mild or asymptomatic phenotypes.
Created: 11 Jun 2018, 10:27 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: CD8A, PanelApp HGNC gene symbol check: CD8A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / CD8-deficiency / CD8 deficiency
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CD8A, GRID_Gene_Symbol: CD8A, GRID_Transcript_ENS_Community submitted: ENST00000409511, GRID_Transcript_RefSeq: NM_001768.6, GRID_Transcript_ENS_used_on_Production: ENST00000409511
Created: 17 Apr 2018, 12:12 p.m.
Source Expert Review Green was added to CD8A. Added phenotypes Susceptibility to respiratory infections associated with CD8alpha chain mutation; Immunodeficiencies affecting cellular and humoral immunity; CD8 deficiency familial, 608957; Recurrent infections, may be asymptomatic for gene: CD8A Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: CD8A was added gene: CD8A was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,IUIS Classification February 2018,Expert Review Amber Mode of inheritance for gene: CD8A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CD8A were set to 11435463; 32086639; 32048120; 17658607 Phenotypes for gene: CD8A were set to Susceptibility to respiratory infections associated with CD8alpha chain mutation; Immunodeficiencies affecting cellular and humoral immunity; CD8 deficiency familial, 608957; Recurrent infections, may be asymptomatic