{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:27:33Z","timestamp":1745468853289,"version":"3.40.4"},"reference-count":0,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytogenet Genome Res"],"published-print":{"date-parts":[[2019]]},"abstract":"<jats:p>We report a patient with developmental delay, brachydactyly type E, short stature, and tetralogy of Fallot. Brachydactyly-mental retardation syndrome (BDMR) was suspected based on the phenotype; however, array CGH excluded a 2q37 deletion, but identified a deletion encompassing the &lt;i&gt;SHOX&lt;\/i&gt; gene. BDMR is characterized by cognitive impairment, skeletal abnormalities involving hands and feet, short stature, and overweight. Most affected individuals carry relatively large 2q37 deletions encompassing &lt;i&gt;HDAC4&lt;\/i&gt;. This gene encodes a histone deacetylase involved in epigenetic regulation of cell growth and differentiation, specifically during endochondral bone formation in chondrocyte hypertrophy. Since &lt;i&gt;SHOX&lt;\/i&gt; haploinsufficiency can cause skeletal defects and short stature but would not fully explain the clinical picture of this patient, exome sequencing was performed, and a heterozygous &lt;i&gt;HDAC8&lt;\/i&gt; frameshift mutation was identified. &lt;i&gt;HDAC8&lt;\/i&gt; is a distinct histone deacetylase involved in cohesin recycling and is responsible for an X-linked dominant Cornelia de Lange-like phenotype. A new blended clinical phenotype may be explained by the result of a dual molecular diagnosis, which represents a combination of 2 independent genetic defects, with relevant implications for genetic counseling, clinical management, and prognosis.<\/jats:p>","DOI":"10.1159\/000499174","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T21:00:34Z","timestamp":1554152434000},"page":"135-140","source":"Crossref","is-referenced-by-count":3,"title":["&lt;b&gt;&lt;i&gt;HDAC8&lt;\/i&gt;&lt;\/b&gt; Loss of Function and &lt;b&gt;&lt;i&gt;SHOX&lt;\/i&gt;&lt;\/b&gt; Haploinsufficiency: Two Independent Genetic Defects Responsible for a Complex Phenotype"],"prefix":"10.1159","volume":"157","author":[{"given":"Giulia","family":"Severi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Bonora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Perri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Scarano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Mazzanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Isidori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Zuntini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soara","family":"Menab\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2018,3,26]]},"container-title":["Cytogenetic and Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499174","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499174","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:26:32Z","timestamp":1745425592000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000499174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,26]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,5,2]]},"published-print":{"date-parts":[[2019,5,7]]}},"URL":"https:\/\/doi.org\/10.1159\/000499174","archive":["Portico"],"relation":{},"ISSN":["1424-8581","1424-859X"],"issn-type":[{"type":"print","value":"1424-8581"},{"type":"electronic","value":"1424-859X"}],"subject":[],"published":{"date-parts":[[2018,3,26]]}}}