Open AccessDiscovery of Digenic Mutation, KCNH2 c.1898A >C and JUP c.916dupA, in a Chinese Family with Long QT Syndrome via Whole-Exome Sequencing
Author(s) -
Yafei Zhai,
Jinxin Miao,
Ying Peng,
Guangming Fang,
Chuchu Wang,
Yaohe Wang,
Xiaoyan Zhao,
Jianzeng Dong
Publication year - 2020
Publication title -
cardiovascular innovations and applications
Language(s) - English
Resource type - Journals
eISSN - 2009-8782
pISSN - 2009-8618
DOI - 10.15212/cvia.2019.0578
Subject(s) - long qt syndrome , exome sequencing , proband , genetics , mutation , sudden cardiac death , herg , short qt syndrome , sudden death , medicine , biology , gene , qt interval , potassium channel
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 fibrillation 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.