{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:34:38Z","timestamp":1789868078740,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009543","name":"Society of Pediatric Psychology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>Cornelia de Lange syndrome (<jats:styled-content style=\"fixed-case\">CdLS<\/jats:styled-content>) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin\u2010related genes <jats:italic><jats:styled-content style=\"fixed-case\">NIPBL<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">SMC1A<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">SMC3<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">RAD21<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">HDAC8<\/jats:styled-content><\/jats:italic>. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in <jats:italic><jats:styled-content style=\"fixed-case\">HDAC8<\/jats:styled-content><\/jats:italic>. Given the high number of variants identified so far, we advise sequencing of <jats:italic><jats:styled-content style=\"fixed-case\">HDAC8<\/jats:styled-content><\/jats:italic> as an indispensable part of the routine molecular diagnostic for patients with <jats:styled-content style=\"fixed-case\">CdLS<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">CdLS<\/jats:styled-content>\u2010overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical <jats:styled-content style=\"fixed-case\">CdLS<\/jats:styled-content> features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X\u2010inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.<\/jats:p>","DOI":"10.1111\/cge.12717","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T09:25:25Z","timestamp":1450257925000},"page":"564-573","source":"Crossref","is-referenced-by-count":39,"title":["Expanding the clinical spectrum of the \u2018<i><scp>HDAC8<\/scp><\/i>\u2010phenotype\u2019 \u2013 implications for molecular diagnostics, counseling and risk prediction"],"prefix":"10.1111","volume":"89","author":[{"given":"I.","family":"Parenti","sequence":"first","affiliation":[{"name":"Sektion f\u00fcr Funktionelle Genetik am Institut f\u00fcr Humangenetik L\u00fcbeck Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gervasini","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Pozojevic","sequence":"additional","affiliation":[{"name":"Sektion f\u00fcr Funktionelle Genetik am Institut f\u00fcr Humangenetik L\u00fcbeck Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.S.","family":"Wendt","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Erasmus MC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Watrin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes, UMR6290\u2010CNRS  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Azzollini","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Braunholz","sequence":"additional","affiliation":[{"name":"Sektion f\u00fcr Funktionelle Genetik am Institut f\u00fcr Humangenetik L\u00fcbeck Universit\u00e4t zu L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Buiting","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik Universit\u00e4tsklinikum D\u00fcsseldorf, Heinrich\u2010Heine\u2010Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Cereda","sequence":"additional","affiliation":[{"name":"U.O.S. 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