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

Rojnueangnit K1, Sirichongkolthong B2, Wongwandee R2, Khetkham T3, Noojarern S4, Khongkraparn A4, Wattanasirichaigoon D4.

Author information

1: Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathumthani, Thailand. rkitiwan@tu.ac.th.
2: Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
3: Divison of Forensic Medicine, Thammasat University Hospital, Pathumthani, Thailand.
4: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract

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.