Targeted deep sequencing analyses of long QT syndrome in a Japanese population

Yuki Nagata, Ryo Watanabe, Christian Eichhorn, Seiko Ohno, Takeshi Aiba, Taisuke Ishikawa, Yukiko Nakano, Yoshiyasu Aizawa, Kenshi Hayashi, Nobuyuki Murakoshi, Tadashi Nakajima, Nobue Yagihara, Hiroyuki Mishima, Takeaki Sudo, Chihiro Higuchi, Atsushi Takahashi, Akihiro Sekine, Takeru Makiyama, Yoshihiro Tanaka, Atsuyuki WatanabeMotomi Tachibana, Hiroshi Morita, Koh Ichiro Yoshiura, Tatsuhiko Tsunoda, Hiroshi Watanabe, Masahiko Kurabayashi, Akihiko Nogami, Yasuki Kihara, Minoru Horie, Wataru Shimizu, Naomasa Makita, Toshihiro Tanaka

Research output: Contribution to journalArticlepeer-review


Long QT syndrome (LQTS) is one of the most common inherited arrhythmias and multiple genes have been reported as causative. Presently, genetic diagnosis for LQTS patients is becoming widespread and contributing to implementation of therapies. However, causative genetic mutations cannot be detected in about 20% of patients. To elucidate additional genetic mutations in LQTS, we performed deep-sequencing of previously reported 15 causative and 85 candidate genes for this disorder in 556 Japanese LQTS patients. We performed in-silico filtering of the sequencing data and found 48 novel variants in 33 genes of 53 cases. These variants were predicted to be damaging to coding proteins or to alter the binding affinity of several transcription factors. Notably, we found that most of the LQTS-related variants in the RYR2 gene were in the large cytoplasmic domain of the N-terminus side. They might be useful for screening of LQTS patients who had no known genetic factors. In addition, when the mechanisms of these variants in the development of LQTS are revealed, it will be useful for early diagnosis, risk stratification, and selection of treatment.

Original languageEnglish
Article numbere0277242
JournalPloS one
Issue number12 December
Publication statusPublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • General


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