{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:36:02Z","timestamp":1779910562665,"version":"3.53.1"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Periodontal Ehlers\u2013Danlos syndrome (pEDS) is a rare condition caused by pathogenic variants in the\n                    <jats:italic>C1R<\/jats:italic>\n                    and\n                    <jats:italic>C1S<\/jats:italic>\n                    genes, encoding subunits C1r and C1s of the first component of the classical complement pathway. It is characterized by early\u2010onset periodontitis with premature tooth loss, pretibial hyperpigmentation and skin fragility. Rare arterial complications have been reported, but venous insufficiency is rarely described. Here we report 13 novel patients carrying heterozygous pathogenic variants in\n                    <jats:italic>C1R<\/jats:italic>\n                    and\n                    <jats:italic>C1S<\/jats:italic>\n                    including three novel\n                    <jats:italic>C1S<\/jats:italic>\n                    variants\n                    <jats:italic>(<\/jats:italic>\n                    c.962G\u2009&gt;\u2009C, c.961\u2009T\u2009&gt;\u2009G and c.961\u2009T\u2009&gt;\u2009A). In addition to the pEDS phenotype, three patients and one relative displayed widespread venous insufficiency leading to persistent varicose leg ulcers. One patient suffered an intracranial aneurysm with familial vascular complications including thoracic and abdominal aortic aneurysm and dissection and intracranial aneurysm rupture. This work confirms that vascular complications can occur, although they are not frequent, which leads us to propose to carry out a first complete non\u2010invasive vascular evaluation at the time of the diagnosis in pEDS patients. However, larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications.\n                  <\/jats:p>","DOI":"10.1111\/cge.13972","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T04:47:28Z","timestamp":1619153248000},"page":"206-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Periodontal (formerly type\n                    <scp>VIII<\/scp>\n                    )\n                    <scp>Ehlers\u2013Danlos<\/scp>\n                    syndrome: Description of 13 novel cases and expansion of the clinical phenotype"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-6570","authenticated-orcid":false,"given":"Salima","family":"El Chehadeh","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), H\u00f4pitaux Universitaires de Strasbourg, H\u00f4pital de Hautepierre  Strasbourg France"},{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale UMRS_1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), Universit\u00e9 de Strasbourg et INSERM  Strasbourg France"},{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U1258, CNRS\u2010UMR7104 Universit\u00e9 de Strasbourg  Illkirch\u2010Graffenstaden France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Legrand","sequence":"additional","affiliation":[{"name":"INSERM, U970, Paris Centre de Recherche Cardiovasculaire Universit\u00e9 de Paris  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares AP\u2010HP, H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Stoetzel","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale UMRS_1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), Universit\u00e9 de Strasbourg et INSERM  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Geoffroy","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale UMRS_1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), Universit\u00e9 de Strasbourg et INSERM  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-8496","authenticated-orcid":false,"given":"Clarisse","family":"Billon","sequence":"additional","affiliation":[{"name":"INSERM, U970, Paris Centre de Recherche Cardiovasculaire Universit\u00e9 de Paris  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares AP\u2010HP, H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-0922","authenticated-orcid":false,"given":"Salma","family":"Adham","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares AP\u2010HP, H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Jeunema\u00eetre","sequence":"additional","affiliation":[{"name":"INSERM, U970, Paris Centre de Recherche Cardiovasculaire Universit\u00e9 de Paris  Paris France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares AP\u2010HP, H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Jaussaud","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine Interne Immunologie Clinique CHRU de Nancy et Universit\u00e9 de Lorraine  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-559X","authenticated-orcid":false,"given":"Jean","family":"Muller","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale UMRS_1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), Universit\u00e9 de Strasbourg et INSERM  Strasbourg France"},{"name":"Laboratoire de Diagnostic G\u00e9n\u00e9tique H\u00f4pitaux Universitaires de Strasbourg, Nouvel H\u00f4pital Civil  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace (IGMA), H\u00f4pitaux Universitaires de Strasbourg, H\u00f4pital de Hautepierre  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karelle","family":"Benistan","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Syndromes d'Ehlers\u2010Danlos non Vasculaires H\u00f4pital Raymond Poincar\u00e9, Garches, Assistance Publique H\u00f4pitaux de Paris  Garches France"},{"name":"UMR U1179 INSERM Universit\u00e9 Versailles Saint\u2010Quentin  Montigny\u2010le\u2010Bretonneux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Gaertner","sequence":"additional","affiliation":[{"name":"Service des Maladies Vasculaires \u2010 Hypertension Art\u00e9rielle H\u00f4pitaux Universitaires de Strasbourg, Nouvel H\u00f4pital Civil  Strasbourg France"},{"name":"Regenerative Nanomedicine INSERM, UMR 1260, FMTS  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Bloch\u2010Zupan","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U1258, CNRS\u2010UMR7104 Universit\u00e9 de Strasbourg  Illkirch\u2010Graffenstaden France"},{"name":"Facult\u00e9 de Chirurgie Dentaire Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"P\u00f4le de M\u00e9decine et Chirurgie Bucco\u2010Dentaires, H\u00f4pital Civil, Centre de R\u00e9f\u00e9rence des Maladies Rares Orales et Dentaires, O\u2010Rares, Fili\u00e8re Sant\u00e9 Maladies Rares TETE COU, European Reference Network ERN CRANIO H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymeric","family":"Courval","sequence":"additional","affiliation":[{"name":"P\u00f4le de M\u00e9decine et Chirurgie Bucco\u2010Dentaires, H\u00f4pital Civil, Centre de R\u00e9f\u00e9rence des Maladies Rares Orales et Dentaires, O\u2010Rares, Fili\u00e8re Sant\u00e9 Maladies Rares TETE COU, European Reference Network ERN CRANIO H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010C\u00e9cile","family":"Mani\u00e8re","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), INSERM U1258, CNRS\u2010UMR7104 Universit\u00e9 de Strasbourg  Illkirch\u2010Graffenstaden France"},{"name":"Facult\u00e9 de Chirurgie Dentaire Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"P\u00f4le de M\u00e9decine et Chirurgie Bucco\u2010Dentaires, H\u00f4pital Civil, Centre de R\u00e9f\u00e9rence des Maladies Rares Orales et Dentaires, O\u2010Rares, Fili\u00e8re Sant\u00e9 Maladies Rares TETE COU, European Reference Network ERN CRANIO H\u00f4pitaux Universitaires de Strasbourg  Strasbourg 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lipsker","sequence":"additional","affiliation":[{"name":"Clinique Dermatologique H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"},{"name":"Facult\u00e9 de M\u00e9decine Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"issue":"2537","key":"e_1_2_7_3_1","first-page":"1","article-title":"C1R mutations trigger constitutive complement 1 activation in periodontal Ehlers\u2010Danlos syndrome","volume":"10","author":"Gr\u00f6bner R","year":"2019","journal-title":"Front 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