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Licensed Unlicensed Requires Authentication Published by De Gruyter September 13, 2017

MEF2C loss-of-function mutation associated with familial dilated cardiomyopathy

Fang Yuan , Zhao-Hui Qiu , Xing-Hua Wang , Yu-Min Sun , Jun Wang , Ruo-Gu Li , Hua Liu , Min Zhang , Hong-Yu Shi , Liang Zhao , Wei-Feng Jiang , Xu Liu , Xing-Biao Qiu , Xin-Kai Qu EMAIL logo and Yi-Qing Yang EMAIL logo



The MADS-box transcription factor myocyte enhancer factor 2C (MEF2C) is required for the cardiac development and postnatal adaptation and in mice-targeted disruption of the MEF2C gene results in dilated cardiomyopathy (DCM). However, in humans, the association of MEF2C variation with DCM remains to be investigated.


The coding regions and splicing boundaries of the MEF2C gene were sequenced in 172 unrelated patients with idiopathic DCM. The available close relatives of the index patient harboring an identified MEF2C mutation and 300 unrelated, ethnically matched healthy individuals used as controls were genotyped for MEF2C. The functional effect of the mutant MEF2C protein was characterized in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system.


A novel heterozygous MEF2C mutation, p.Y157X, was detected in an index patient with adult-onset DCM. Genetic screen of the mutation carrier’s family members revealed that the mutation co-segregated with DCM, which was transmitted as an autosomal dominant trait with complete penetrance. The non-sense mutation was absent in 300 control individuals. Functional analyses unveiled that the mutant MEF2C protein had no transcriptional activity. Furthermore, the mutation abolished the synergistic transactivation between MEF2C and GATA4 as well as HAND1, two other transcription factors that have been associated with DCM.


This study indicates MEF2C as a new gene responsible for human DCM, which provides novel insight into the mechanism underpinning DCM, suggesting potential implications for development of innovative prophylactic and therapeutic strategies for DCM, the most prevalent form of primary myocardial disease.

Corresponding authors: Dr. Xin-Kai Qu, Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, P.R. China, Phone: +86 21 62821990, Fax: +86 21 62821105


We are really grateful to the study participants for their devotion to the investigation.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was partially supported by grants from the National Natural Science Fund of China (81470372 and 81370400); the Experimental Animal Program of Shanghai, China (16140901602); the key program for Basic Research of Shanghai, China (14JC1405500); the Natural Science Fund of Shanghai, China (14ZR1438000 and 15ZR1438100); and the key project of Shanghai Chest Hospital, China (2014YZDH10102).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2017-5-24
Accepted: 2017-8-11
Published Online: 2017-9-13
Published in Print: 2018-2-23

©2018 Walter de Gruyter GmbH, Berlin/Boston

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