| A novel genetic variant in the transcription factor Islet-1 exerts gain of function on myocyte enhancer factor 2C promoter activity. | |
| | |
MedLine Citation:
|
PMID: 23152444 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
AIMS: 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-Dreifuss muscular dystrophy (EDMD). METHODS AND RESULTS: 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'-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. CONCLUSION: 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. |
| | |
Authors:
|
Felix W Friedrich; Gilles Dilanian; Patricia Khattar; Denise Juhr; Lucie Gueneau; Philippe Charron; Véronique Fressart; Jean-Thomas Vilquin; Richard Isnard; Laurent Gouya; Pascale Richard; Naima Hammoudi; Michel Komajda; Gisèle Bonne; Thomas Eschenhagen; Olivier Dubourg; Eric Villard; Lucie Carrier |
Related Documents
:
|
23437964 - Suggestive evidence for association between l-type voltage-gated calcium channel (cacna... 23756484 - The unexpected role of copy number variations in juvenile myoclonic epilepsy. 23040034 - Lack of association between picalm rs3851179 polymorphism and alzheimer's disease in ch... 23559864 - Pharmacogenetic association with early response to intravitreal ranibizumab for age-rel... 21564754 - Microsatellite markers isolated from drosophila hydei. 10468914 - Prevalence of ras mutations in thyroid neoplasia. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-11-14 |
Journal Detail:
|
Title: European journal of heart failure Volume: - ISSN: 1879-0844 ISO Abbreviation: Eur. J. Heart Fail. Publication Date: 2012 Nov |
Date Detail:
|
Created Date: 2012-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 100887595 Medline TA: Eur J Heart Fail Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany and DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: IGF1 dependence of dietary energy balance effects on murine MET1 mammary tumor progression, epitheli...
Next Document: Retroaortic abscess: an unusual complication of a retained epicardial pacing wire.