Primary immunodeficiency or monogenic inflammatory bowel disease
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
Source NHS GMS was added to C4B.
Source North West GLH was added to C4B.
Source London North GLH was added to C4B.
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 C4B were set to C4B deficiency, 614379, SLE predisposition, 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
IUIS Classification February 2018 was added to C4B. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to C4B. Panel: Primary immunodeficiency disorders
Gene: c4b has been classified as Green List (High Evidence).
Gene: c4b has been classified as Green List (High Evidence).
Phenotypes for gene: C4B were set to C4B deficiency, 614379; SLE predisposition
Phenotypes for gene: C4B were set to C4B deficiency, 614379
Publications for gene: C4B were set to 2355198; 12626442; 2788199; 19062096; 1569346
Expert Review Amber was added to C4B. Panel: Primary immunodeficiency disorders
Phenotypes for gene C4B were set to C4B deficiency
C4B was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
C4B was created by Louise Daugherty