Ehlers Danlos syndrome with a likely monogenic cause
Gene: C1SComment on phenotypes: Previous phenotypes:
Ehlers-Danlos syndrome periodontal type 2, 617174;Periodontal Ehlers-Danlos syndrome;Periodontal EDS;pEDS;EDS type VIIICreated: 18 Mar 2021, 1:35 p.m. | Last Modified: 18 Mar 2021, 1:35 p.m.
Panel Version: 2.15
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: C1S; Suggested initial gene rating: greenCreated: 3 Apr 2019, 3:41 p.m.
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, 2:07 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 literatureCreated: 25 Apr 2017, 12:52 p.m.
Comment on list classification: Awaiting expert review on whether this can be made GreenCreated: 7 Apr 2017, 10:18 a.m.
Comment on phenotypes: reordered listCreated: 7 Apr 2017, 10:16 a.m.
Comment on phenotypes: added OMIM phenotypeCreated: 7 Apr 2017, 10:15 a.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 2 unrelated families of 9 affected individuals and identified heterozygosity for missense or in-frame insertion/deletion mutations in the C1S gene. It was found that the variants 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 C1S variants identified in pEDS-affected individuals appeared to have gain-of-function effects.Created: 7 Apr 2017, 10:07 a.m.
Periodontal EDS is a distinct clinical entity shown to be caused by alterations in the genes C1S and C1R, 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: 7 Apr 2017, 9:57 a.m.
In relation to the EDS pathogenetic scheme, C1S 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: 7 Apr 2017, 9:56 a.m.
Comment on phenotypes: added synonymsCreated: 30 Mar 2017, 10:22 a.m.
Added gene 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, 10:20 a.m.
This is a rare dominant form of EDSCreated: 30 Mar 2017, 10:12 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Periodontal Ehlers-Danlos syndrome; Periodontal EDS (pEDS)
Publications
Phenotypes for gene: C1S were changed from Ehlers-Danlos syndrome periodontal type 2, 617174; Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS; EDS type VIII to Ehlers-Danlos syndrome, periodontal type, 2, OMIM:617174
Source NHS GMS was added to C1S. Rating Changed from Green List (high evidence) to Green List (high evidence)
25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Phenotypes for C1S were set to Ehlers-Danlos syndrome periodontal type 2, 617174;Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS; EDS type VIII
Phenotypes for C1S were set to Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS; EDS type VIII; Ehlers-Danlos syndrome periodontal type 2, 617174
Publications for C1S were set to 27745832; 28306229; 28306225
Phenotypes for C1S were set to Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS; EDS type VIII; Ehlers– Danlos Syndrome periodontitis type
Phenotypes for C1S were set to Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS; EDS type VIII; Ehlers– Danlos Syndrome periodontitis type; Ehlers–Danlos Syndrome periodontosis type
Phenotypes for C1S were set to Periodontal Ehlers-Danlos syndrome; Periodontal EDS; pEDS;EDS type VIII;Ehlers– Danlos Syndrome periodontitis type;Ehlers–Danlos Syndrome periodontosis type.
Phenotypes for C1S were set to Periodontal Ehlers-Danlos syndrome;Periodontal EDS;pEDS
C1S was added to Ehlers-Danlos syndromespanel. Sources: Literature
C1S was created by LouiseD