Clinical and genetic analysis of a Chinese pedigree affected with Type 2 Long QT syndrome due to variant of KCNH2 gene
10.3760/cma.j.cn511374-20231010-00179
- VernacularTitle:KCNH2基因变异致2型长QT综合征一个家系的临床及遗传学分析
- Author:
Haitao YANG
1
;
Meng SUN
;
Jingjing LIU
;
Xiaosheng CHEN
;
Xizheng XU
;
Juan HU
;
Lijie YAN
;
Jintao WU
Author Information
1. 郑州大学华中阜外医院 阜外华中心血管病医院心内科，郑州 451464
- Keywords:
Type 2 long QT syndrome;
Whole exome sequencing;
KCNH2 gene;
Regulation of membrane potential
- From:
Chinese Journal of Medical Genetics
2024;41(10):1218-1224
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome (LQTS).Methods:A pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23, 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out for the proband, and candidate variant was screened through functional annotation and protein-protein interaction (PPI) analysis. Sanger sequencing was conducted to verify the pathogenicity of candidate variant. This study was approved by Medical Ethics Committee of the Fuwai Central China Cardiovascular Hospital (Ethics No. 2019-15).Results:WES revealed that the proband has harbored a missense variant of the KCNH2 gene, namely c. 1478A>G (p.Tyr493Cys), which was confirmed by Sanger sequencing to have inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_supporting+ PM5+ PP3+ PP4). Conclusion:The KCNH2 gene c. 1478A>G (p.Tyr493Cys) variant probably underlay the type 2 LQTS in this pedigree.
