Whole-Exome Sequencing Reveals Novel Genetic Variation for Dilated Cardiomyopathy in Pediatric Chinese Patients

  • Genyin Dai
  • Zhening Pu
  • Xueying Cheng
  • Jie Yin
  • Jun Chen
  • Ting Xu
  • Han Zhang
  • Zewei Li
  • Xuan Chen
  • Jinlong Chen
  • Yuming QinEmail author
  • Shiwei YangEmail author
Original Article


Dilated cardiomyopathy (DCM) is characterized by left or bilateral ventricular dilation and systolic dysfunction without rational conditions, which can lead to progressive heart failure and sudden cardiac death. Most of the pathogenic genes have been reported in adult population by locus mapping in familial cases and animal model studies. However, it still remains challenging to decipher the role of genetics in the etiology of pediatric DCM. We applied whole-exome sequencing (WES) for 30 sporadic pediatric DCM subjects and 100 non-DCM local controls. We identified the pathogenic mutations using bioinformatics tools based on genomic strategies synergistically and confirmed mutations by Sanger sequencing. We identified compound heterozygous nonsense mutations in DSP (c.3799C > T, p.R1267X; c.4444G > T, p.E1482X). In sporadic cases, the two heterozygous mutations in XIRP2 were identified. Then we performed an exome-wide association study with 30 case and 100 control subjects. Interestingly, we could not identify TTN truncating variants in all cases. Collectively, we observed a significant risk signal between carriers of TTN deleterious missense variants and DCM risk (odds ratio 4.0, 95% confidence interval 1.1–22.2, p = 3.12 × 10−2). Our observations expanded the spectrum of mutations and were valuable in the pre- and postnatal screening and genetic diagnosis for DCM.


Pediatric dilated cardiomyopathy Clinical genetics Whole-exome sequencing TTN mutations Compound mutations 



The authors thank all the participating families and patients for their contributions.


This work was supported by the National Natural Science Foundation of China (81670284), Nanjing Science and Technology Project (201715057), Nanjing Medical Science and technique Development Foundation, Nanjing Department of Health (QRX17024, ZKX13037). The authors confirm that the funders had no influence over the study design, content of the article, or selection of this journal.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics Approval and Consent to Participate

The ethical committee of the Children’s Hospital of Nanjing Medical University approved of this study for human research, and written informed consents were obtained from all DCM patients and legal guardians.

Consent for Publication

Permissions were received from the patients whose photographs are to be published.

Supplementary material

246_2019_2096_MOESM1_ESM.docx (323 kb)
Supplementary material 1 (DOCX 323 kb). Fig. A1: The workflow of DCM genetic analysis. Abbreviations: MAF, minor allele frequency; UTR, untranslated region; Inheritance models: Autosomal recessive, De novo and Compound heterozygotes manner. Fig. A2: Sanger chromatograms of XIRP2 mutations


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyChildren’s Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Center of Clinical ResearchWuxi People’s Hospital of Nanjing Medical UniversityWuxiChina
  3. 3.Department of EchocardiographyChildren’s Hospital of Nanjing Medical UniversityNanjingChina

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