Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: C1R
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
Autosomal dominant mutations in same gene cause Periodontal Ehlers Danlos syndrome, see PMID 27745832Created: 19 Jun 2018, 6:09 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SLE; pyogenic infections
Publications
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
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): C1R .PanelApp HGNC gene symbol check: C1R . IUIS Disease: C1r deficiency . IUIS Inheritance: AR .T cells: Increased DN T cells , .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms, Ehlers Danlos phenotype . IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed from Amber to Green due to expert review. It is noted that SLE; pyogenic infections are biallelic and that monoallelic forms result different phenotype, and this is reflected in the Ehlers-Danlos syndromes panelCreated: 20 Jun 2018, 3:26 p.m.
Comment on phenotypes: added phenotypes from external reviewCreated: 20 Jun 2018, 3:25 p.m.
Comment on publications: added publications suggested from external expert review to support upgrading of the gene to GreenCreated: 20 Jun 2018, 3:24 p.m.
Keep Amber for now, more suitable for autoinflammatory spectrum panel? Seek external clinical review.Created: 15 Jun 2018, 3:24 p.m.
past onto clinical team for further review, early complement deficiency type does not result in a significant increased susceptibility to infection rather, patients develop autoimmune complications, particularly systemic lupus erythematosus (SLE)- associated with EDS phenotype and in particularly is associated to general Immunodeficiency due to a classical component pathway complement deficiency - however I am not sure if there are enough cases and specific variants? Seems to be more with risk and susceptibility than pertinence of a PID phenotype eg: there seem to be a number of other associated phenotypesCreated: 15 Jun 2018, 1:36 p.m.
The incidence of SLE is 90% for C1q, 75% for C4, and 55% for C1r and C1s deficiency. This increased risk may be explained by that fact that C1q is important for the clearance of immune complexes and apoptotic cells.Created: 15 Jun 2018, 1:23 p.m.
added early onset tagCreated: 15 Jun 2018, 1:02 p.m.
Comment on publications: PMID:27745832 Kapferer-Seebacher et al. (2016) studies Ehlers-Danlos syndrome periodontal type 2 patients with mutations in the C1R or C1S genes (77 and 16 patients, respectively) . In addition to the predominate phenotypes associated to periodontal type EDS, about half of patients exhibited atrophic scars or wide scarring and/or prominent vasculature. Other variable features included recurrent infections, joint pain, flat feet, marfanoid facial features, scoliosis, osteoarthritis, and hernias. A minority of patients had joint dislocations; aneurysms occurred in 4 families, and autoimmune disorders occurred in 1 family. PMID: 28544690 (2017) studied a large consanguineous family from Turkey findings revealed a novel high-penetrance mutation in C1R as the cause of monogenic SLE. Disease expressivity in this family appears to be influenced by additional common and rare genetic variants.Created: 15 Jun 2018, 1 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 downloaded from ESID Registry. ESID_Gene_original: C1r, PanelApp HGNC gene symbol check: C1R, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement component 1 deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: C1R, GRID_Gene_Symbol: C1R, GRID_Transcript_ENS_Community submitted: ENST00000542285, GRID_Transcript_RefSeq: NM_001733, GRID_Transcript_ENS_used_on_Production: ENST00000542285Created: 17 Apr 2018, 12:12 p.m.
Publications
Publications for gene C1R were updated from 27745832; 29795138; 28711143; 21784777; 28544690 to 28544690; 21784777; 27745832; 29795138; 28711143
Source NHS GMS was added to C1R.
Source North West GLH was added to C1R.
Source London North GLH was added to C1R.
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 C1R were set to C1r/C1s deficiency, combined, Lupus, Complement component 1 deficiency, Immunodeficiency due to a classical component pathway complement deficiency, SLE, pyogenic infections, SLE, infections with encapsulated organisms, Ehlers Danlos phenotype, Complement Deficiencies
IUIS Classification February 2018 was added to C1R. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to C1R. Panel: Primary immunodeficiency disorders
Gene: c1r has been classified as Green List (High Evidence).
Gene: c1r has been classified as Green List (High Evidence).
Phenotypes for gene: C1R were set to C1r/C1s deficiency, combined, Lupus; Complement component 1 deficiency; Immunodeficiency due to a classical component pathway complement deficiency; SLE; pyogenic infections
Publications for gene: C1R were set to 27745832; 29795138; 28711143; 21784777; 28544690
Gene: c1r has been classified as Green List (High Evidence).
Phenotypes for gene: C1R were set to C1r/C1s deficiency, combined, Lupus; Complement component 1 deficiency; Immunodeficiency due to a classical component pathway complement deficiency
Phenotypes for gene: C1R were set to C1r/C1s deficiency, combined, Lupus; Complement component 1 deficiency; Immunodeficiency due to a classical component pathway complement deficiency; Ehlers-Danlos syndrome, periodontal type1, 130080
Phenotypes for gene: C1R were set to C1r/C1s deficiency, combined, Lupus; Complement component 1 deficiency; Immunodeficiency due to a classical component pathway complement deficiency; Ehlers-Danlos syndrome, periodontal type1, 130080
Gene: c1r has been classified as Amber List (Moderate Evidence).
Gene: c1r has been classified as Green List (High Evidence).
Publications for gene: C1R were set to 27745832; 29795138; 28711143
Publications for gene: C1R were set to 27745832; 29795138
Phenotypes for gene: C1R were set to C1r/C1s deficiency, combined, Lupus; Complement component 1 deficiency; Immunodeficiency due to a classical component pathway complement deficiency
Expert Review Amber was added to C1R. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to C1R. Panel: Primary immunodeficiency disorders Phenotypes for gene C1R were set to C1r/C1s deficiency, combined, Lupus, Complement component 1 deficiency
Phenotypes for gene C1R were set to C1r/C1s deficiency, combined, Lupus
C1R was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
C1R was created by Louise Daugherty