Identification of Gene Mutations in Primary Pediatric Cardiomyopathy by Whole Exome Sequencing

  • Kitiwan RojnueangnitEmail author
  • Boonchu Sirichongkolthong
  • Ratthapon Wongwandee
  • Thanitchet Khetkham
  • Saisuda Noojarern
  • Arthaporn Khongkraparn
  • Duangrurdee Wattanasirichaigoon
Original Article


Pediatric primary cardiomyopathy is rare but serious, having high mortality; hypertrophic and dilated types are the most common. Its etiology has been mainly considered idiopathic; however, next generation sequencing techniques have revealed nearly half of idiopathic pediatric cases arose from specific genetic mutations. Therefore, our study aimed to identify the genetic causes of primary idiopathic cardiomyopathy. Newborns to 15-year old patients with this condition were recruited between March 2016 and May 2017 at Thammasat University Hospital. Complete patient history and physical examination data were collected by a geneticist with cardiac examinations and echocardiograms by pediatric cardiologists. Whole exome sequencing was performed for all. Of the 12 patients enrolled, 5 cases were dilated type and 7 hypertrophic. Two with dilated type were excluded during follow-up as cause was determined (hypocalcemia and pacemaker induced). A list of 118 genes for cardiomyopathy was analyzed in the remaining 10 cases. Pathogenic and likely pathogenic mutations were identified in 5 patients: HRAS, PTPN11, SOS1, FLNC and TXNRD2; half our patients were not actually idiopathic. Despite its high cost, genetic testing is useful for determining familial risk as well as predicting patient cardiomyopathy progress.


Primary cardiomyopathy Whole exome sequencing Pediatric Mutations 



We would like to thank patients and families who were part of this study, the Faculty of Medicine, Thammasat University for providing funding (Grant TP.2-10/2559); and Faculty of Medicine Ramathibodi Hospital, Mahidol University for providing Research Career Award to DW during the time of this study. We also thank Ms Debra Kim Liwiski, writer/international instructor, the Clinical Research Center, Faculty of Medicine, Thammasat University for language editing.

Author Contributions

KR designed the study, performed and interpreted the genetic tests and wrote the manuscript. BS and RW performed echocardiograms and reviewed the manuscript. TK performed genetic testing. SN and AK reviewed the whole exome results, and DW supervised overall concepts designed and edited the manuscript.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in the present study involving human participants were in accordance with the ethical standards of the Human Research Ethics Committee of Thammasat University No.1 (Faculty of Medicine: MTU-EC-PE-1-191/58) and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual parents and assent from participants (if possible) included in the study.

Supplementary material

246_2019_2240_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)


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Copyright information

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

Authors and Affiliations

  • Kitiwan Rojnueangnit
    • 1
    Email author
  • Boonchu Sirichongkolthong
    • 1
  • Ratthapon Wongwandee
    • 1
  • Thanitchet Khetkham
    • 2
  • Saisuda Noojarern
    • 3
  • Arthaporn Khongkraparn
    • 3
  • Duangrurdee Wattanasirichaigoon
    • 3
  1. 1.Department of Pediatrics, Faculty of MedicineThammasat UniversityPathumthaniThailand
  2. 2.Divison of Forensic MedicineThammasat University HospitalPathumthaniThailand
  3. 3.Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Ramathibodi HospitalMahidol UniversityBangkokThailand

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