{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:13:02Z","timestamp":1792203182356,"version":"4.4.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>\n            Background\u2003Congenital thrombotic thrombocytopaenic purpura (TTP) or Upshaw\u2013Schulman syndrome (USS) is a rare, life-threatening, inherited thrombotic microangiopathy (TMA). USS is mostly due to bi-allelic recessive sequence variations of the a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) gene inducing a severe ADAMTS13 deficiency (activity\u2009&lt;\u200910 IU\/dL). In healthy individuals, ADAMTS13 circulates in a folded conformation where CUB domains interact with the spacer domain. The spacer\u2013CUB interaction is abrogated when ADAMTS13 is conformationally activated.<\/jats:p><jats:p>\n            Objective\u2003This article evaluates the influence of ADAMTS13 sequence variations on both clinical\/biological phenotype and ADAMTS13 conformation in USS.<\/jats:p><jats:p>\n            Patients and Methods\u2003All USS patients from the French registry for TMAs (1 January 2000 to 1 June 2017) were investigated for ADAMTS13 genotype, phenotype (activity, antigen and autoantibodies) and conformation. Clinical records were analysed (inaugural acute TTP and follow-up). Child-onset USS was compared with adult-onset USS.<\/jats:p><jats:p>\n            Results\u2003Fifty-six USS patients from 51 families (34 child-onset and 22 adult-onset cases) were enrolled. Child-onset USS was characterized by a large panel of ADAMTS13 sequence variations (n\u2009=\u200943), spread all over ADAMTS13 gene and not correlated with either clinical features or plasmatic ADAMTS13 parameters. In contrast, adult-onset USS, consisting exclusively in pregnancy-induced TTP, included a smaller and distinct panel of ADAMTS13 sequence variations (n\u2009=\u200920) because of one mutation (p.Arg1060Trp) present in 82% of patients. ADAMTS13 conformation was studied in 16 USS patients (5 child-onset and 11 adult-onset USS, encompassing 16 distinct ADAMTS13 sequence variations) whose ADAMTS13 antigen levels were detectable: 14 of 16 patients (87.5%) exhibited abnormalities of ADAMTS13 conformation.<\/jats:p><jats:p>\n            Conclusion\u2003In USS, age-onset defines two entities and ADAMTS13 sequence variations modify ADAMTS13 conformation.<\/jats:p>","DOI":"10.1055\/s-0038-1673686","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T22:50:19Z","timestamp":1539384619000},"page":"1902-1917","source":"Crossref","is-referenced-by-count":62,"title":["ADAMTS13 Gene Mutations Influence ADAMTS13 Conformation and Disease Age-Onset in the French Cohort of Upshaw\u2013Schulman Syndrome"],"prefix":"10.1055","volume":"118","author":[{"given":"B\u00e9rang\u00e8re","family":"Joly","sequence":"additional","affiliation":[{"name":"Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris Diderot, H\u00f4pital Saint-Louis, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"Service d'H\u00e9matologie Biologique, Universit\u00e9 Paris Diderot, H\u00f4pital Lariboisi\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Boisseau","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital H\u00f4tel-Dieu, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elien","family":"Roose","sequence":"additional","affiliation":[{"name":"Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Kulak Campus Kortrijk, KU Leuven, Kortrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Stepanian","sequence":"additional","affiliation":[{"name":"Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris Diderot, H\u00f4pital Saint-Louis, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"Service d'H\u00e9matologie Biologique, Universit\u00e9 Paris Diderot, H\u00f4pital Lariboisi\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Biebuyck","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique, H\u00f4pital Necker, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Hogan","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique, H\u00f4pital Robert Debr\u00e9, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Provot","sequence":"additional","affiliation":[{"name":"Service de n\u00e9phrologie, CHRU de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahsou","family":"Delmas","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie, CHU Pellegrin, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Garrec","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital H\u00f4tel-Dieu, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vanhoorelbeke","sequence":"additional","affiliation":[{"name":"Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Kulak Campus Kortrijk, KU Leuven, Kortrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Coppo","sequence":"additional","affiliation":[{"name":"D\u00e9partement d'H\u00e9matologie Clinique, Universit\u00e9 Pierre et Marie Curie, H\u00f4pital Saint-Antoine, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Veyradier","sequence":"additional","affiliation":[{"name":"Institut Universitaire d'H\u00e9matologie, Universit\u00e9 Paris Diderot, H\u00f4pital Saint-Louis, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"Service d'H\u00e9matologie Biologique, Universit\u00e9 Paris Diderot, H\u00f4pital Lariboisi\u00e8re, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the French Reference Center for Thrombotic Microangiopathies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2018,10,12]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0038-1673686.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T21:11:09Z","timestamp":1557177069000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0038-1673686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,12]]},"references-count":0,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,10,24]]},"published-print":{"date-parts":[[2018,11]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0038-1673686","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,12]]}}}