Ehlers Danlos syndrome with a likely monogenic cause

Gene: C1R

Comment on phenotypes: Previous phenotypes:
Ehlers-Danlos syndrome periodontal type 1, 130080;Periodontal Ehlers-Danlos syndrome;Periodontal EDS;pEDS;EDS type VIII;Ehlers-Danlos Syndrome periodontitis type;EDSVIII;EDSPD1

Created: 18 Mar 2021, 1:34 p.m. | Last Modified: 18 Mar 2021, 1:34 p.m.

Panel Version: 2.14

Green List (high evidence)

I don't know

This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: C1R; Suggested initial gene rating: green

Created: 3 Apr 2019, 3:41 p.m.

Green List (high evidence)

Green List (high evidence)

Green List (high evidence)

Review from Dr Anthony Vandersteen, IWK Health centre in Halifax, Nova Scotia, Canada - 'I would shift the pEDS genes (C1R C1S) to green, lots of patients and no doubt about it'

Created: 25 Apr 2017, 2:06 p.m.

Comment on list classification: changed status from Amber to Green due to expert review comments from Dr Anthony Vandersteen and evidence in the literature

Created: 25 Apr 2017, 12:46 p.m.

Comment on publications: Added publication to support number of cases to date with Periodontal Ehlers-Danlos syndrome. Kapferer-Seebacher et al., 2016 (PMID:27745832) reported 15 unrelated families of 76 affected individuals (which included 8 cases previously reported) and identified heterozygosity for missense or in-frame insertion/deletion mutations in the C1R gene. It was found that the mutations segregated with disease in the families and neither was found in the ExAC, 1000 Genomes Project, ClinVar, or dbSNP (March 2016) databases. It was noted that heterozygous C1R variants identified in pEDS-affected individuals appeared to have gain-of-function effects.

Created: 7 Apr 2017, 10:08 a.m.

Awaiting expert review on whether this can be made Green

Created: 6 Apr 2017, 3:57 p.m.

Periodontal EDS is a distinct clinical entity shown to be caused by alterations in the genes C1R and C1S, the genes encode complement 1 subunits C1r and C1s.The cardinal clinical feature is severe early-onset periodontitis with marked gingival recessions that in some individuals affects primary teeth. In contrast to individuals with non-syndromic chronic or aggressive periodontitis, those with pEDS have strikingly thin and fragile oral soft tissue with absence of attached gingiva (PMID:28306225).

Created: 6 Apr 2017, 3:28 p.m.

Comment on phenotypes: Added more phenotypes form Orphanet and OMIM

Created: 6 Apr 2017, 1:08 p.m.

In relation to the EDS pathogenetic scheme, C1R belongs to 'Disorders of complement pathway'. The scheme regroups EDS subtypes for which the proteins, coded by the causative genes, function within the same pathway, and which are likely to have shared pathogenic mechanisms, based on current knowledge.

Created: 6 Apr 2017, 12:31 p.m.

Comment on phenotypes: added synonyms

Created: 30 Mar 2017, 10:24 a.m.

This is a rare dominant form of EDS

Created: 30 Mar 2017, 10:12 a.m.

Added from 2017 International Classification of the Ehlers–Danlos Syndromes (PMID:28306229) and The Ehlers–Danlos Syndromes, rare types (PMID:28306225).
To be reviewed further for consideration as a Green gene.

Created: 30 Mar 2017, 10:11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Periodontal Ehlers-Danlos syndrome; Periodontal EDS (pEDS)

Publications

• 27745832
• 28306229
• 28306225