{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T09:09:11Z","timestamp":1771060151007,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T00:00:00Z","timestamp":1485388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Kleefstra Syndrome (<jats:styled-content style=\"fixed-case\">KS<\/jats:styled-content>) (<jats:styled-content style=\"fixed-case\">MIM<\/jats:styled-content># 610253) is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase\u20101 (<jats:italic><jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>1, <\/jats:italic><jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>). <jats:italic><jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>1<\/jats:italic> (<jats:styled-content style=\"fixed-case\">MIM<\/jats:styled-content># 607001) encodes a histone methyltransferase that heterodimerizes with <jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>2 (also known as G9a, <jats:styled-content style=\"fixed-case\">MIM<\/jats:styled-content># 604599), which together are responsible for mono\u2010 and dimethylation of H3 lysine 9 (H3K9me1 and \u2010me2), resulting in transcriptional repression of target genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This report describes an 18\u2010year\u2010old woman with intellectual disability, severely limited speech, hypotonia, microcephaly, and facial dysmorphisms, who was found to have a novel <jats:italic>de novo<\/jats:italic> single\u2010base frameshift deletion in <jats:italic><jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Functional studies using patient fibroblasts showed decreased H3K9me2 compared to wild\u2010type control cells, thus providing a rapid confirmatory test that complements molecular studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whole exome sequencing revealed a novel frameshift deletion in <jats:italic><jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>1<\/jats:italic> after a lengthy diagnostic odyssey in this patient. Functional testing using this patient's fibroblasts provides proof\u2010of\u2010concept for the analysis of variants of uncertain significance that are predicted to impact <jats:styled-content style=\"fixed-case\">EHMT<\/jats:styled-content>1 enzymatic activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.268","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T05:09:06Z","timestamp":1485407346000},"page":"141-146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A novel <i>de novo<\/i> frameshift deletion in <i><scp>EHMT<\/scp>1<\/i> in a patient with Kleefstra Syndrome results in decreased H3K9 dimethylation"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-1275","authenticated-orcid":false,"given":"Patrick R.","family":"Blackburn","sequence":"first","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Jacksonville Florida 32224"},{"name":"Department of Health Science Research Mayo Clinic Jacksonville Florida 32224"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot A.","family":"Cousin","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Health Science Research Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole J.","family":"Boczek","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Health Science Research Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey J.","family":"Beek","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwen A.","family":"Lomberk","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenetics and Chromatin Dynamics Mayo Clinic Rochester Minnesota 55901"},{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul A.","family":"Urrutia","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenetics and Chromatin Dynamics Mayo Clinic Rochester Minnesota 55901"},{"name":"Division of Gastroenterology and Hepatology Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dusica","family":"Babovic\u2010Vuksanovic","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Health Science Research Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota 55901"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds490"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000058"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.012"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/505693"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.062950"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815627880"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005963"},{"key":"e_1_2_6_10_1","unstructured":"Rasband W.S. 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