Abstract
Long QT syndrome (LQTS) is a rare inherited arrhythmia disease characterized by a prolonged QT interval on 12-lead electrocardiograms. It is the crucial factor to induce syncope, ventricular fibrillation, and even sudden cardiac death. Previous studies have proved that mutations of ion channels-related genes play an important role in LQTS patients. In this study, we enrolled a Chinese family with LQTS and syncope. With the help of whole-exome sequencing, we identified a novel nonsense mutation (c.439C>T/p.Q147X) of Ring Finger Protein 207 (RNF207) in this family. The novel mutation, resulting in a premature stop codon in exon 4 of the RNF207 gene, co-segregated with the affected individuals. Bioinformatics analysis and real-time PCR further proved that the newly identified mutation might induce nonsense-mediated mRNA decay. In mutation carriers, the level of RNF207 mRNA expression was much lower than controls, which may affect potassium channel KCNH2 and lead to LQTS and syncope. In this research, we reported a rare novel mutation of RNF207 in LQTS and syncope patients which further supports the significant role of RNF207 in potassium channel activation and expanded the spectrum of RNF207 mutations. These data may contribute to the genetic diagnosis and counseling of families with LQTS and syncope.
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We thank all subjects for participating in this study. This study was supported by the National Natural Science Foundation of China (81370394 and 81500359).
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Fan, LL., Chen, YQ., Huang, H. et al. Exome sequencing identifies a novel nonsense mutation of Ring Finger Protein 207 in a Chinese family with Long QT syndrome and syncope. J Hum Genet 64, 233–238 (2019). https://doi.org/10.1038/s10038-018-0549-1
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DOI: https://doi.org/10.1038/s10038-018-0549-1
