Discovery of Digenic Mutation, KCNH2 c.1898A > C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing  

作　　者：Yafei Zhai Jinxin Miao Ying Peng Guangming Fang Chuchu Wang Yaohe Wang Xiaoyan Zhao Jianzeng Dong 

机构地区：[1]Department of Cardiology,The First Affi liated Hospital,Zhengzhou University,Zhengzhou,Henan 450052,P.R.China [2]Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou,Henan 450046,P.R.China [3]College of Life Sciences,Zhengzhou University,Zhengzhou,Henan 450000,P.R.China [4]Sino-British Research Center for Molecular Oncology,National Center for the International Research in Cell and Gene Therapy,School of Basic Sciences,Academy of Medical Sciences,Zhengzhou University,Zhengzhou,Henan 450052,P.R.China [5]Beijing Anzhen Hospital,Capital Medical University,Beijing,China

出　　处：《Cardiovascular Innovations and Applications》2020年第2期257-267,共11页心血管创新与应用（英文）

基　　金：the National Key R&D Plan under grant no.2018YFC1312505 to Xiaoyan Zhao and the Henan University of Chinese Medicine under grant no.00104311-2019-55 to Jinxin Miao.

摘　　要：Long QT syndrome(LQTS),which is caused by an ion channel–related gene mutation,is a malignant heart disease with a clinical course of a high incidence of ventricular fi brillation and sudden cardiac death in the young.Mutations in KCNH2(which encodes potassium voltage-gated channel subfamily H member 2)are responsible for LQTS in many patients.Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing.The c.916dupA mutation in JUP(which encodes junction plakoglobin)is also discovered.Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy.The double mutation in the proband may help explain his severe clinical manifestations,such as sudden cardiac death at an early age.Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line,while the mutation in JUP came from his maternal line.The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.

关 键 词：Long QT syndrome(LQTS) Digenic mutation KCNH2 JUP 

分 类 号：R54[医药卫生—心血管疾病]