In PloS one ; h5-index 176.0
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.
Nagata Yuki, Watanabe Ryo, Eichhorn Christian, Ohno Seiko, Aiba Takeshi, Ishikawa Taisuke, Nakano Yukiko, Aizawa Yoshiyasu, Hayashi Kenshi, Murakoshi Nobuyuki, Nakajima Tadashi, Yagihara Nobue, Mishima Hiroyuki, Sudo Takeaki, Higuchi Chihiro, Takahashi Atsushi, Sekine Akihiro, Makiyama Takeru, Tanaka Yoshihiro, Watanabe Atsuyuki, Tachibana Motomi, Morita Hiroshi, Yoshiura Koh-Ichiro, Tsunoda Tatsuhiko, Watanabe Hiroshi, Kurabayashi Masahiko, Nogami Akihiko, Kihara Yasuki, Horie Minoru, Shimizu Wataru, Makita Naomasa, Tanaka Toshihiro
2022
