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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A novel genetic variant in the transcription factor Islet-1 exerts gain of function on myocyte enhancer factor 2C promoter activity
European Journal of Heart Failure, Volume 15, No. 3, Year 2013
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Description
AimsThe 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-Dreifuss muscular dystrophy (EDMD).Methods and resultsThe 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'-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 ∼4-fold higher in the presence of wild-type and ∼6-fold higher in the presence of mutant ISL1 in both HEK and CHO cells.ConclusionThis 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. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved.
Authors & Co-Authors
Friedrich, Felix W.
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Dilanian, Gilles
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Khattar, Patricia
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Juhr, Denise
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Gueneau, Lucie
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Charron, Philippe H.
France, Paris
Inserm
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Fressart, Véronique
France, Paris
Inserm
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Vilquin, Jean Thomas
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Isnard, Richard N.
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Gouya, Laurent
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Richard, Pascale
France, Paris
Inserm
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Hammoudi, Naima
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Algeria, Algiers
Ehs en Cardiologie Maouche Mohand Amokrane Ex-cnms
Komajda, Michel
France, Paris
Inserm
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Bonne, Giséle
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Eschenhagen, Thomas
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Dubourg, Olivier
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Villard, Eric
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
Carrier, Lucie
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
France, Paris
Inserm
France, Boulogne-billancourt
Hopital Ambroise Pare, Boulogne-billancourt
France, Paris
Sorbonne Université
Statistics
Citations: 23
Authors: 18
Affiliations: 6
Identifiers
Doi:
10.1093/eurjhf/hfs178
ISSN:
13889842
e-ISSN:
18790844
Research Areas
Cancer
Disability
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases
Study Design
Cohort Study