一个Liddle综合征新SCNN1B基因移码突变的鉴定  

Identification of a novel frameshift mutation in the SCNN1B causing Liddle syndrome

作　　者：曲艺 卢伊婷 张迪 刘欣畅 范鹏 陈洁欣 张涵波 杨坤璂 田涛 周怡 张琼钰 张钰 王林平 黄卓 刘亚欣 胡爱华 周宪梁 Yi Qu;Yiting Lu;Di Zhang;Xinchang Liu;Peng Fan;Jiexin Chen;Hanbo Zhang;Kunqi Yang;Tao Tian;Yi Zhou;Qiongyu Zhang;Yu Zhang;Linping Wang;Zhuo Huang;Yaxin Liu;Aihua Hu;Xianliang Zhou(Department of Cardiology,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China;State Key Laboratory of Natural and Biomimetic Drugs,Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China;Institute of Laboratory Animal Sciences,Comparative Medicine Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Emergency and Critical Care Center,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China;Department of Non-Communicable Disease Management,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China;Hypertension Center,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China)

机构地区：[1]Department of Cardiology,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China [2]State Key Laboratory of Natural and Biomimetic Drugs,Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China [3]Institute of Laboratory Animal Sciences,Comparative Medicine Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [4]Emergency and Critical Care Center,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China [5]Department of Non-Communicable Disease Management,Beijing Children’s Hospital,Capital Medical University,National Center for Children’s Health,Beijing 100045,China [6]Hypertension Center,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China

出　　处：《Science Bulletin》2023年第4期383-387,M0003,共6页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2016YFC1300100);the National Natural Science Foundation of China(81974042);the CAMS Innovation Fund for Medical Sciences(2022-I2M-C&T-A-010,2022I2M-C&T-A-011,and 2022-I2M-C&T-B-041);the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019XK320057 and 2019XK320058)。

摘　　要：Liddle综合征是一种由编码肾小管上皮细胞钠离子通道(ENa Cs)的SCNN1A、SCNN1B及SCNN1G基因突变引起的罕见单基因遗传性高血压,基于基因检测技术进行确诊并及时给予对应治疗可显著改善患者预后.由于发病率低,相关突变位点报道少,目前Liddle综合征突变位点谱仍不完善.本研究通过对野生型及突变型ENa Cs重组非洲爪蟾卵母细胞进行膜片钳检测,首次确定了SCNN1B基因中一个移码突变c.1691_1693delins G对Liddle综合征的致病性.进一步研究结果表明,突变型非洲爪蟾卵母细胞ENa Cs电流显著增加,这与已知的Liddle综合征发病机制一致.此外,本研究通过对该家系中接受阿米洛利/氢氯噻嗪复方制剂治疗的7名患者进行为期12个月的观察研究,发现所有患者血压控制理想,血清钾离子、血浆肾素及醛固酮水平正常,无心血管事件及严重药物不良反应发生.本研究有助于扩大Liddle综合征的基因诊断谱,并为该病的治疗方案提供参考.Hypertension is a cardiovascular disease that seriously threatens public health worldwide.Early and effective control of blood pressure can prevent the occurrence of stroke,coronary heart disease,kidney disease,etc.[1,2].The influence of genetic factors on hypertension has been confirmed multiple times,and targeted medication according to genetic testing remains a challenge for hypertension treatment at present[3].

关 键 词：血浆肾素 阿米洛利 醛固酮水平 非洲爪蟾卵母细胞 移码突变 基因检测技术 心血管事件 基因诊断 

分 类 号：R764[医药卫生—耳鼻咽喉科]