Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome
| العنوان: | Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome |
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| المؤلفون: | Chen Sun, Ning Li, Qian-Qian Wang, Lu-Yi Yan, Shuai-Kang Ba, Shan-Shan Zhang, Qiu-Xia He, Xi-Qiang Chen, Wei-Li Gong, Qing Zhu, Ke-Chun Liu |
| المصدر: | Physiological Genomics. 54:141-152 |
| بيانات النشر: | American Physiological Society, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Physiology, Genetics |
| الوصف: | Sick sinus syndrome (SSS) is a term used for a variety of disorders defined by abnormal cardiac impulse formation and by abnormal propagation from the heart’s sinoatrial node. In this study, we present a case from a Chinese family in which two closely related individuals had the symptoms and electrocardiographic evidence of SSS. We hypothesized that multiple individuals affected by the disease in the family was an indication of its genetic predisposition, and thus performed high-throughput sequencing for the participants from the family to detect potential disease-associated variants. One of the potential variants that was identified was a KCNG2 gene variant (NC_000018.9: g.77624068_77624079del). Further bioinformatic analysis showed that the observed variant may be a pathogenic mutation. The results of protein-protein docking and whole cell patch-clamp measurements implied that the deletion variant in KCNG2 could affect its binding the KV2.1 protein, and finally affect the function of Kv channel, which is an important determinant in regulation of heartbeat. Therefore, we inferred that the variable KCNG2 gene may affect the function of Kv channel by changing the binding conformation of KCNG2 and KV2.1 proteins and then adversely affect propagation from the sinoatrial node and cardiac impulse formation by changing the action potential repolarization of heart cells. In summary, our findings suggested that the dominant KCNG2 deletion variant in the examined Chinese family with SSS may be a potential disease-associated variant. |
| تدمد: | 1531-2267 1094-8341 7762-4068 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::615920bccca808508486a67d8e0fa71e https://doi.org/10.1152/physiolgenomics.00132.2021 |
| رقم الأكسشن: | edsair.doi...........615920bccca808508486a67d8e0fa71e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15312267 10948341 77624068 |
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