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J Hum Genet. 2018 Sep;63(9):989-996. doi: 10.1038/s10038-018-0479-y. Epub 2018 Jun 15.

Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy.

Author information

1
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. takehayashi@tulip.ocn.ne.jp.
2
Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo, 160-8582, Japan. takehayashi@tulip.ocn.ne.jp.
3
Genome laboratory, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
4
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
5
Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan.
6
Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
7
Department of Therapeutic Strategy for Severe Heart Failure, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
8
Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan.
9
Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. akitis@mri.tmd.ac.jp.

Abstract

Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) present a high risk for sudden cardiac death in pediatric patients. The aim of this study was to identify disease-associated genetic variants in Japanese patients with pediatric HCM and RCM. We analyzed 67 cardiomyopathy-associated genes in 46 HCM and 7 RCM patients diagnosed before 16 years of age using a next-generation sequencing system. We found that 78% of HCM and 71% of RCM patients carried disease-associated genetic variants. Disease-associated genetic variants were identified in 80% of HCM patients with a family history and in 77% of HCM patients with no apparent family history (NFH). MYH7 and/or MYBPC3 variants comprised 76% of HCM-associated variants, whereas troponin complex-encoding genes comprised 75% of the RCM-associated variants. In addition, 91% of HCM patients with implantable cardioverter-defibrillators and infant cases had NFH, and the 88% of HCM patients carrying disease-associated genetic variants were males who carried MYH7 or MYBPC3 variants. Moreover, two disease-associated LAMP2, one DES and one FHOD3 variants, were identified in HCM patients. In this study, pediatric HCM and RCM patients were found to carry disease-associated genetic variants at a high rate. Most of the variants were in MYH7 or MYPBC3 for HCM and TNNT2 or TNNI3 for RCM.

PMID:
29907873
DOI:
10.1038/s10038-018-0479-y
[Indexed for MEDLINE]

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