{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:15Z","timestamp":1790524875824,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>The tenascin\u2010X (<jats:styled-content style=\"fixed-case\">TNX<\/jats:styled-content>) deficient type Ehlers\u2013Danlos syndrome (<jats:styled-content style=\"fixed-case\">EDS<\/jats:styled-content>) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the <jats:italic>TNXB gene<\/jats:italic>, the <jats:styled-content style=\"fixed-case\">TNX<\/jats:styled-content>\u2010deficient type <jats:styled-content style=\"fixed-case\">EDS<\/jats:styled-content> is probably to be under diagnosed. We therefore performed an observational, cross\u2010sectional study. History and physical examination were performed. Results of serum <jats:styled-content style=\"fixed-case\">TNX<\/jats:styled-content> measurements were collected and mutation analysis was performed by a combination of next\u2010generation sequencing (<jats:styled-content style=\"fixed-case\">NGS<\/jats:styled-content>), Sanger sequencing and multiplex ligation\u2010dependent probe amplification (<jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content>). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. <jats:styled-content style=\"fixed-case\">TNX<\/jats:styled-content> serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non\u2010sense <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> mediated decay. In short, patients with the <jats:styled-content style=\"fixed-case\">TNX<\/jats:styled-content>\u2010deficient type <jats:styled-content style=\"fixed-case\">EDS<\/jats:styled-content> typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of <jats:italic>TNXB<\/jats:italic> in a diagnostic setting is challenging.<\/jats:p>","DOI":"10.1111\/cge.12853","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T11:23:52Z","timestamp":1472729032000},"page":"411-425","source":"Crossref","is-referenced-by-count":52,"title":["Recognizing the tenascin\u2010X deficient type of Ehlers\u2013Danlos syndrome: a cross\u2010sectional study in 17 patients"],"prefix":"10.1111","volume":"91","author":[{"given":"S.","family":"Demirdas","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Centre  Rotterdam the Netherlands"},{"name":"Department of Human Genetics Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Dulfer","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Genetics Guy's and St Thomas' Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kempers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"van Beek","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Centre for Connective Tissue Research VU University Medical Centre  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Micha","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Centre for Connective Tissue Research VU University Medical Centre  Amsterdam the 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Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Centre for Connective Tissue Research VU University Medical Centre  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.C.","family":"Voermans","sequence":"additional","affiliation":[{"name":"Department of Neurology Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-104"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa002939"},{"issue":"5","key":"e_1_2_7_5_1","first-page":"160","article-title":"A 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