COVID-19 research
Gene: C4B
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
Complete C4 deficiency is associated with susceptibility to invasive infection and SLECreated: 19 Jun 2018, 6:48 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SLE predisposition
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): C4A+C4B .PanelApp HGNC gene symbol check: C4B . IUIS Disease: Complete C4 deficiency . IUIS Inheritance: AR .T cells: Very low, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed Amber to Green from external review comment and further publications to support gene-disease associationCreated: 20 Jun 2018, 3:39 p.m.
changed to Green, external expert review notes Complete C4 deficiency is associated with susceptibility to invasive infection and SLECreated: 20 Jun 2018, 3:39 p.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.Created: 20 Jun 2018, 3:38 p.m.
Leave as Amber for external clinical review, conflicting evidence regarding microbial infectionCreated: 15 Jun 2018, 4:31 p.m.
Complete or partial C4B deficiencies has been related to vulnerability and severity of microbial infection PMID: 2355198, 12626442, 2788199). However in PMID:19062096 and PMID:1569346 could not confirm thisCreated: 15 Jun 2018, 4:25 p.m.
Complete C4 deficiency requires four null alleles and is rarely found, but is highly associated with SLE (75% incidence). Partial C4 deficiencies with one to three null alleles, however, are relatively common, found in up to 25% of individuals. Complete C4A deficiency is greatly over-represented in the SLE population. C4A deficiencies are found in about 1% of the general population and 10–15% of patients with SLE. Complete C4B deficiency has been associated with bacterial infections, suggesting that the functionally of different C4 genes, C4A and C4B contribute differently to host defense and autoimmunity (PMID:2788199, 2355198). However, Cates et al. (1009) PMID:1569346 could not confirm this association, and showed that C4B deficiency is not associated with meningitis or bacteremia with encapsulated bacteria was no increase in homozygous C4B deficiency among patients with bacteremia or meningitis caused by encapsulated bacteria. PMID: 19062096 (2009) no relation was found between C4 isotypic deficiencies and meningitis, in agreement with the results of Cates et al. (1992), but they noted the chort was small.Created: 15 Jun 2018, 3:54 p.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: C4B, GRID_Gene_Symbol: C4B, GRID_Transcript_ENS_Community submitted: ENST00000435363, GRID_Transcript_RefSeq: NM_001002029.3, GRID_Transcript_ENS_used_on_Production: ENST00000435363Created: 17 Apr 2018, 12:12 p.m.
Publications
gene: C4B was added gene: C4B was added to Viral susceptibility. Sources: Expert Review Green,Victorian Clinical Genetics Services,North West GLH,GRID V2.0,NHS GMS,London North GLH,IUIS Classification February 2018 Mode of inheritance for gene: C4B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C4B were set to 12626442; 2355198; 19062096; 1569346; 2788199 Phenotypes for gene: C4B were set to C4B deficiency, 614379; SLE, infections with encapsulated organisms , partial deficiency is common (either C4A or C4B) and appears to have a modest effect on host defense; Complement Deficiencies; SLE predisposition