{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:52:11Z","timestamp":1771473131703,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T00:00:00Z","timestamp":1503273600000},"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":[[2018,1]]},"abstract":"<jats:p>Deletions encompassing <jats:styled-content style=\"fixed-case\">TAK1<\/jats:styled-content>\u2010binding protein 2 (<jats:italic><jats:styled-content style=\"fixed-case\">TAB2<\/jats:styled-content><\/jats:italic>) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole\u2010exome sequencing (WES) disclosed the novel <jats:italic><jats:styled-content style=\"fixed-case\">TAB2<\/jats:styled-content><\/jats:italic> c.1398dup (p.<jats:styled-content style=\"fixed-case\">Thr467Tyrfs<\/jats:styled-content>*6) variant that eliminates the C\u2010terminal zinc finger domain essential for activation of <jats:styled-content style=\"fixed-case\">TAK1<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">TGF\u03b2<\/jats:styled-content>\u2010activated kinase 1)\u2010dependent signaling pathways. The sporadic case carryed a ~2\u2009Mb de novo deletion including 28 genes also comprising <jats:italic><jats:styled-content style=\"fixed-case\">TAB2<\/jats:styled-content><\/jats:italic>. This study reveal an association between <jats:italic><jats:styled-content style=\"fixed-case\">TAB2<\/jats:styled-content><\/jats:italic> mutations and a phenotype resembling Ehlers\u2010Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with <jats:italic><jats:styled-content style=\"fixed-case\">TAB2<\/jats:styled-content><\/jats:italic> perturbations and emphasize the role of <jats:styled-content style=\"fixed-case\">TAK1<\/jats:styled-content> signaling network in human development.<\/jats:p>","DOI":"10.1111\/cge.13032","type":"journal-article","created":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T04:02:50Z","timestamp":1491537770000},"page":"126-133","source":"Crossref","is-referenced-by-count":22,"title":["A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with <i><scp>TAB2<\/scp><\/i> mutations"],"prefix":"10.1111","volume":"93","author":[{"given":"M.","family":"Ritelli","sequence":"first","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine University of Brescia  Brescia 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