ArticleAmerican journal of human genetics2016
Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Pooled it
- Microfibril Denudation Marks Early Aortic Vulnerability in SMAD3 Variant Carriers: A Multigenerational Study.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Comprehensive Prediction Analysis of Novel Noncoding Regulatory Variants Identified in the MicroRNA Binding Regions in Complement System Genes.International journal of molecular sciences · 2026Article
- Regulatory effects of beta-2-microglobulin on reactive oxygen species generation in polymorphonuclear cells.Scientific reports · 2026Article
- Fascial Pathophysiology in Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome: A Review of Emerging Evidence.International journal of molecular sciences · 2025Review
- Impact of a Heterozygous C1RCells · 2025Article
- Genetic risk variants implicate impaired maintenance and repair of periodontal tissues as causal for periodontitis-A synthesis of recent findings.Periodontology 2000 · 2025Review
- Exosome-mediated regulation of inflammatory pathway during respiratory viral disease.Virology journal · 2024Review
- The role of cutaneous manifestations in the diagnosis of the Ehlers-Danlos syndromes.Skin health and disease · 2023Review
- Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.Frontiers in genetics · 2023Article
- Degradation of collagen I by activated C1s in periodontal Ehlers-Danlos Syndrome.Frontiers in immunology · 2023Article
- Oral characteristics in adult individuals with periodontal Ehlers-Danlos syndrome.Journal of clinical periodontology · 2022Article
- Multifocal periapical cemental dysplasia in periodontal Ehlers-Danlos syndrome combined with leukoencephalopathy in the mutation of c.890G > a, G297D [pEDS].Clinical case reports · 2022Article
- The yin and the yang of early classical pathway complement disorders.Clinical and experimental immunology · 2022Review
- Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis.International journal of molecular sciences · 2022Article
- Exome Sequencing of 5 Families with Severe Early-Onset Periodontitis.Journal of dental research · 2022Article
- Review
- Mechanobiology in the Comorbidities of Ehlers Danlos Syndrome.Frontiers in cell and developmental biology · 2022Review
- Transcriptome Analysis of Monocytes and Fibroblasts Provides Insights Into the Molecular Features of Periodontal Ehlers-Danlos Syndrome.Frontiers in genetics · 2022Article
- Complement System and Alarmin HMGB1 Crosstalk: For Better or Worse.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
40 authors at 20 institutions in 9 countries.
Funding
Abstract
Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.
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