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Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy


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.

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We thank Yukiko Ueda and Chinami Sonobe for their excellent technical assistance with respect to NGS and Sanger sequencing. We are also grateful to the following doctors for blood sampling and clinical examinations: Tsuguya Sakamoto (Hanzomon Hospital, Tokyo, Japan), Sachio Kawai (Juntendo University, Tokyo, Japan), Hirofumi Nishi (Kurume University, Fukuoka, Japan), Keiko Kawano, Seigo Okada and Masahiko Harada (Yamaguchi University, Yamaguchi, Japan), Yoshimiki Kiyohara (Kobe University, Kobe, Japan), Takeshi Tana (Ryukyu University, Okinawa, Japan), Kazuhiro Mori (Tokushima University, Tokushima, Japan), Hitoshi Koito (Kansai Medical University, Hyogo, Japan), Yo Niida (Kanazawa Medical University, Kanazawa, Japan), Tdaaki Abe and Kanae Noritake (National Cerebral and Cardiovascular Center, Osaka, Japan), Atsuhito Takeda (Hokkaido University, Hokkaido, Japan), Junji Toyama (Nagoya Heart Center, Aichi, Japan), Takuro Arimura (Kagoshima University, Kagoshima, Japan), Taisuke Ishikawa (Nagasaki University, Nagasaki, Japan), Hironori Murakami (Teine Keijinkai Hospital, Hokkaido, Japan), and Fukiko Ichida (Toyama University, Toyama, Japan). This research was supported by Japan Society for the Promotion of Science KAKENHI grant number 26460407 (T.H.), 17K08684 (T.H.), 15K15095 (A.K.) and 16H05296 (A.K.), a grant from THE INSTITUTE OF SEIZON AND LIFE SCIENCES (T.H), and Nanken-Kyoten, TMDU.

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Correspondence to Takeharu Hayashi or Akinori Kimura.

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Hayashi, T., Tanimoto, K., Hirayama-Yamada, K. et al. Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy. J Hum Genet 63, 989–996 (2018).

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