{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T17:56:48Z","timestamp":1768931808983,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The transcription factor Islet-1 (ISL1) is a marker of cardiovascular progenitors and is essential for mammalian cardiogenesis. An ISL1 haplotype has recently been associated with congenital heart disease. In this study we evaluated whether ISL1 variants are associated with hypertrophic (HCM), dilated (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), or with Emery\u2013Dreifuss muscular dystrophy (EDMD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The six exon and intron boundaries of ISL1 were screened for genetic variants in a cohort of 454 index cases. Eleven exonic variants were identified in HCM, DCM, ARVC, and\/or EDMD. Out of the five novel variants, two are located in the 5\u2019-untranslated region, two are silent (p.Arg171Arg and p.Asn189Asn), and one is a missense (p.Asn252Ser). The latter was identified in the homozygous state in one DCM patient, and in the heterozygous state in 11 relatives, who did not present with DCM but often with cardiovascular features. This variant was found in one HCM patient also carrying a MYH7 mutation and in 3\/96 North-African Caucasian control individuals, but was absent in 138 European Caucasian control individuals. We investigated the effect of the ISL1 wild type and p.Asn252Ser mutant on myocyte enhancer factor 2C (Mef2c) promoter activity, an established ISL1 target. Mef2c promoter activity was \u223c4-fold higher in the presence of wild-type and \u223c6-fold higher in the presence of mutant ISL1 in both HEK and CHO cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study describes a new gain-of-function p.Asn252Ser variant in the human ISL1 gene, which could potentially lead to greater activation of downstream targets involved in cardiac development, dilation, and hypertrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfs178","type":"journal-article","created":{"date-parts":[[2012,11,14]],"date-time":"2012-11-14T20:30:37Z","timestamp":1352925037000},"page":"267-276","source":"Crossref","is-referenced-by-count":18,"title":["A Novel Genetic Variant in the Transcription Factor Islet-1 Exerts Gain of Function on Myocyte Enhancer Factor 2C Promoter Activity"],"prefix":"10.1093","volume":"15","author":[{"given":"Felix W.","family":"Friedrich","sequence":"first","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf and DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Dilanian","sequence":"additional","affiliation":[{"name":"INSERM, U956 , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Khattar","sequence":"additional","affiliation":[{"name":"INSERM, U974; CNRS, UMR7215; UPMC UM 76; Institut de Myologie , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Juhr","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf and DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Gueneau","sequence":"additional","affiliation":[{"name":"INSERM, U974; CNRS, UMR7215; UPMC UM 76; Institut de Myologie , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Charron","sequence":"additional","affiliation":[{"name":"INSERM, U956 , Paris ,","place":["France"]},{"name":"AP-HP, Institut de Cardiologie, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Fressart","sequence":"additional","affiliation":[{"name":"INSERM, U956 , Paris ,","place":["France"]},{"name":"AP-HP, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Thomas","family":"Vilquin","sequence":"additional","affiliation":[{"name":"INSERM, U974; CNRS, UMR7215; UPMC UM 76; Institut de Myologie , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Isnard","sequence":"additional","affiliation":[{"name":"AP-HP, Institut de Cardiologie, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]},{"name":"UPMC Universit\u00e9 Paris 06, IFR14 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Gouya","sequence":"additional","affiliation":[{"name":"AP-HP, Service de Cardiologie, H\u00f4pital Ambroise Par\u00e9 , Boulogne ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Richard","sequence":"additional","affiliation":[{"name":"INSERM, U956 , Paris ,","place":["France"]},{"name":"AP-HP, UF Cardiog\u00e9n\u00e9tique et Myog\u00e9n\u00e9tique, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naima","family":"Hammoudi","sequence":"additional","affiliation":[{"name":"Service de Cardiologie, EHS Maouche (ex. 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Hamburg-Eppendorf and DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Dubourg","sequence":"additional","affiliation":[{"name":"AP-HP, Institut de Cardiologie, Groupe Hospitalier Piti\u00e9-Salp\u00eatri\u00e8re , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Villard","sequence":"additional","affiliation":[{"name":"INSERM, U956 , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Carrier","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf and DZHK (German Centre for Cardiovascular Research), partner site Hamburg\/Kiel\/L\u00fcbeck , Hamburg ,","place":["Germany"]},{"name":"INSERM, U974; 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