{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:08:54Z","timestamp":1791119334941,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In most patients, the genetic cause of isolated GH deficiency (IGHD) is unknown. By identifying several genes associated with height variability within the normal population, three separate genome-wide association studies provided new candidate genes for human growth disorders. We selected two of them for genetic screening of our IGHD population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>We aimed to determine whether high-mobility group A2 (<jats:italic>HMGA2<\/jats:italic>) and cyclin-dependent protein kinase 6 (<jats:italic>CDK6<\/jats:italic>) are involved in the pathogenicity of IGHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We directly sequenced coding regions and exon\u2013intron boundaries of the genes<jats:italic>HMGA2<\/jats:italic>and<jats:italic>CDK6<\/jats:italic>in 105 Caucasian IGHD patients from the Dutch HYPOPIT study. In addition, we developed a new probe set of multiplex ligation-dependent probe amplification for both genes in order to detect copy number variations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In one patient with classical IGHD phenotype, we identified a new heterozygous 20\u200abp deletion in the intronic region of<jats:italic>HMGA2<\/jats:italic>(c.250-29_-9del), which was absent in the databases and healthy controls. Together, with recently published data concerning the 12q14 microdeletion syndrome, where patients with an<jats:italic>HMGA2<\/jats:italic>haploinsufficiency had proportionate short stature, this study provides further support of the important role for HMGA2 in growth. In<jats:italic>CDK6<\/jats:italic>, we found only known polymorphisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides the first report of a deletion in the<jats:italic>HMGA2<\/jats:italic>gene that might be related to IGHD. We suggest that this gene is investigated as a second screening in patients with a classical IGHD phenotype in which mutations in classical candidate genes have been excluded.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-11-0478","type":"journal-article","created":{"date-parts":[[2011,7,30]],"date-time":"2011-07-30T02:42:10Z","timestamp":1311993730000},"page":"537-544","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Isolated GH deficiency: mutation screening and copy number analysis of HMGA2 and CDK6 genes"],"prefix":"10.1093","volume":"165","author":[{"given":"Darya","family":"Gorbenko Del Blanco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C G","family":"de Graaff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Posthouwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo J","family":"Visser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita C S","family":"Hokken-Koelega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"1_40809643","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nrendo.2010.147","volume":"6","year":"2010","journal-title":"NATURE REVIEWS ENDOCRINOLOGY"},{"issue":"5","key":"2_36732399","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1210\/jc.2009-2139","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"1","key":"3_15537278","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0022-3476(94)70117-2","volume":"125","author":"Lindsay","year":"1994","journal-title":"The Journal of pediatrics","ISSN":"https:\/\/id.crossref.org\/issn\/0022-3476","issn-type":"print"},{"issue":"1","key":"4_14667869","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1210\/jc.78.1.11","volume":"78","author":"Phillips","year":"1994","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"10","key":"5_30011605","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1038\/ng2121","volume":"39","author":"Weedon","year":"2007","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"5","key":"6_30990663","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/ng.121","volume":"40","author":"Weedon","year":"2008","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"5","key":"7_30990661","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/ng.125","volume":"40","author":"Lettre","year":"2008","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"5","key":"8_30990662","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/ng.122","volume":"40","author":"Gudbjartsson","year":"2008","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"7317","key":"9_38218747","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1038\/nature09410","volume":"467","author":"Lango Allen","year":"2010","journal-title":"Nature; Physical Science (London)","ISSN":"https:\/\/id.crossref.org\/issn\/1476-4687","issn-type":"print"},{"issue":"1","key":"10_39082322","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ajhg.2010.11.007","volume":"88","author":"Lanktree","year":"2011","journal-title":"American journal of human genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9297","issn-type":"print"},{"issue":"1","key":"11_16980346","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/gcc.10018","volume":"34","author":"Hauke","year":"2002","journal-title":"Genes, chromosomes &amp; cancer","ISSN":"https:\/\/id.crossref.org\/issn\/1045-2257","issn-type":"print"},{"issue":"1","key":"12_18886253","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbaexp.2005.03.006","volume":"1729","author":"Hauke","year":"2005","journal-title":"Biochimica et Biophysica Acta. 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