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Primary immunodeficiency

Gene: C1R

Green List (high evidence)

C1R (complement C1r)
EnsemblGeneIds (GRCh38): ENSG00000159403
EnsemblGeneIds (GRCh37): ENSG00000159403
OMIM: 613785, Gene2Phenotype
C1R is in 4 panels

4 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

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

Tracy Briggs (Manchester Genomic Medicine Centre)

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Autosomal dominant mutations in same gene cause Periodontal Ehlers Danlos syndrome, see PMID 27745832
Created: 19 Jun 2018, 6:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SLE; pyogenic infections

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Added publication referenced by IUIS december 2019 update
Created: 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/A
Created: 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 panel
Created: 20 Jun 2018, 3:26 p.m.
Comment on phenotypes: added phenotypes from external review
Created: 20 Jun 2018, 3:25 p.m.
Comment on publications: added publications suggested from external expert review to support upgrading of the gene to Green
Created: 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 phenotypes
Created: 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 tag
Created: 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 deficiency
Created: 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: ENST00000542285
Created: 17 Apr 2018, 12:12 p.m.

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • 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
Tags
early-onset
OMIM
613785
Clinvar variants
Variants in C1R
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Feb 2020, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene C1R were updated from 27745832; 29795138; 28711143; 21784777; 28544690 to 28544690; 21784777; 27745832; 29795138; 28711143

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to C1R.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to C1R.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to C1R.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

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

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to C1R. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to C1R. Panel: Primary immunodeficiency disorders

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c1r has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c1r has been classified as Green List (High Evidence).

20 Jun 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

20 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: C1R were set to 27745832; 29795138; 28711143; 21784777; 28544690

20 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c1r has been classified as Green List (High Evidence).

15 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

15 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

15 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

15 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c1r has been classified as Amber List (Moderate Evidence).

15 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: c1r has been classified as Green List (High Evidence).

15 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: C1R were set to 27745832; 29795138; 28711143

15 Jun 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: C1R were set to 27745832; 29795138

1 Jun 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to C1R. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

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

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene C1R were set to C1r/C1s deficiency, combined, Lupus

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

C1R was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

C1R was created by Louise Daugherty