{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:11:17Z","timestamp":1783959077126,"version":"3.55.0"},"reference-count":24,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T00:00:00Z","timestamp":1741392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T00:00:00Z","timestamp":1741392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"abstract":"<jats:p>Introduction: Variants in the intron splicing enhancer (ISE) of intron 3 in the GH1 gene are implicated in the etiology of isolated growth hormone deficiency type 2 (type II IGHD). Methods: Exome sequencing was performed to screen variants that co-segregated with IGHD in an extended family with type II IGHD. The causality of the candidate variant was assessed using bioinformatic tools and previous in vitro studies. Results: Exome sequencing identified a rare intronic variant (NM_000515.5, c.291+34 G&gt;A) in the second XGGG repeat of ISE in intron 3 of GH1, which occurred de novo in the mother with IGHD and was passed onto her two affected children. The variant was previously shown in vitro to cause exon 3 skipping in 50% of the mRNAs and was predicted to create a new binding site for exonic splicing enhancer binding proteins (SR proteins). Conclusion: Our familial case reiterates the importance of intronic variants in the splicing enhancer region as a cause of IGHD. Consideration should be given to sequencing the splicing enhancer region in intron 3 of GH1 for patients who undergo genetic testing for growth hormone deficiency.<\/jats:p>","DOI":"10.1159\/000545037","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T12:00:56Z","timestamp":1741435256000},"page":"762-772","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Variant in an Intron Splicing Enhancer Associated with Familial Growth Hormone Deficiency"],"prefix":"10.1159","volume":"99","author":[{"given":"Sally","family":"Radovick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Gangat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7227-5925","authenticated-orcid":false,"given":"Youn Hee","family":"Jee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,3,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2783"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.147"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1067"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.v2i2.52"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1054\/ghir.1999.0126"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1280"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1261\/rna.876308"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.9.1491"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.79.5.7962317"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.80.12.8530604"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.6.909"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12887"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073774"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.24.9225-9235.2000"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.8.7757"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.46.125"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1159\/000341766"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2002.610310.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2377"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.002"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/hrp\/article-pdf\/doi\/10.1159\/000545037\/4349487\/000545037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000545037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:01:20Z","timestamp":1783958480000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000545037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,8]]},"references-count":24,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,7,13]]},"published-print":{"date-parts":[[2026,7,22]]}},"URL":"https:\/\/doi.org\/10.1159\/000545037","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.28558208","asserted-by":"subject"}]},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,8]]}}}