Article
Biochemistry & Molecular Biology
Yu-Wen Cheng, Chia-Tung Wu, Chi-Jen Chang, Yung-Hsin Yeh, Gwo-Jyh Chang, Hsin-Yi Tsai, Lung-An Hsu
Summary: Through whole-exome sequencing, we identified a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Functional expression of the mutant K channel was restored by lowering temperature and using potassium channel inhibitors or openers. Our study reveals the mechanisms underlying LQT2 and offers potential therapeutic avenues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Hong Wen, Lixiang Sun, Jiaqi Zhong, Fujian Wu
Summary: Long-QT syndrome type 2 (LQT2) is a severe disease caused by genetic variants in KCNH2. Researchers generated a human embryonic stem cell line with a LQT2 related mutation in KCNH2, which exhibited stem cell characteristics and could be used for disease modeling and investigating pathological mechanisms.
STEM CELL RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Takanori Aizawa, Yuko Wada, Kanae Hasegawa, Hai Huang, Tomohiko Imamura, Jingshan Gao, Asami Kashiwa, Hirohiko Kohjitani, Megumi Fukuyama, Koichi Kato, Eri Toda Kato, Takashi Hisamatsu, Seiko Ohno, Takeru Makiyama, Takeshi Kimura, Minoru Horie
Summary: This study aimed to investigate the clinical phenotypes of LQT2 patients, with one-third of the patients carrying KCNH2 non-missense variants resulting in haploinsufficiency (HI). These patients exhibited milder phenotypes. The remaining two-thirds of patients had missense variants causing trafficking deficiency and resulting in either haploinsufficiency (HI) or dominant-negative (DN) effects. Through molecular mechanism studies, we were able to better predict the clinical outcomes in the patients.
Article
Medical Laboratory Technology
Kelan Zha, Qiang Ye
Summary: This case report describes a 22-year-old woman who experienced frequent syncopal episodes after childbirth, with genetic analysis revealing a new mutation in the KCNH2 gene shared by her and her family members. This mutation is the first reported case of a KCNH2 mutation at this site.
ANNALS OF CLINICAL AND LABORATORY SCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Haoyang Lu, Wen Ding, Hui Xiao, Manyu Dai, Yangcheng Xue, Zhuoran Jia, Jie Guo, Mengzuo Wu, Bing Shen, Ren Zhao
Summary: In this study, we report a missense mutation P441L in the C-terminus of KCNQ1 gene, which leads to a severe LQT1 phenotype in a 37-year-old female patient. Variant P441L shows reduced membrane trafficking and interaction with KCNQ1-KCNE1, resulting in potassium efflux disorder and eventually causing LQT1.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Peter M. Kekenes-Huskey, Don E. Burgess, Bin Sun, Daniel C. Bartos, Ezekiel R. Rozmus, Corey L. Anderson, Craig T. January, Lee L. Eckhardt, Brian P. Delisle
Summary: The electrocardiogram has revolutionized the diagnosis of heart disease and arrhythmias by allowing noninvasive measurement of the heart's electrical activity. In the study of long QT syndrome (LQTS), significant progress has been made, including the establishment of the International LQTS Registry, the development of a phenotypic scoring system, identification of major genes associated with LQTS, and the formulation of guidelines for patient management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Lixiang Sun, Jiaqi Zhong, Fujian Wu, Furong Li, Xiaofei Yang, Zhiyu Zeng
Summary: The pathogenesis of LQT2 caused by hERG deficiency is still unclear due to the lack of suitable animal and human models. In this study, a human embryonic stem cell line carrying a LQTS-related mutation in KCNH2 was generated and demonstrated the characteristics of stem cells and the ability to differentiate into all three germ layers.
STEM CELL RESEARCH
(2022)
Article
Biology
Rebeca Lorca, Alejandro Junco-Vicente, Alicia Perez-Perez, Isaac Pascual, Yvan Rafael Persia-Paulino, Francisco Gonzalez-Urbistondo, Elias Cuesta-Llavona, Barbara C. Fernandez-Barrio, Cesar Moris, Jose Manuel Rubin, Eliecer Coto, Juan Gomez, Jose Julian Rodriguez Reguero
Summary: Long QT syndrome is a genetic disease associated with malfunction of ion channels in cardiomyocytes, leading to ventricular arrhythmias and sudden death. This study identified a new pathogenic variant and described its phenotypic characteristics. The findings showed a high prevalence and low adherence to medical treatment in affected families, with a high rate of clinical events.
Article
Physiology
Lettine van den Brink, Karina O. Brandao, Loukia Yiangou, Albert Blanch-Asensio, Mervyn P. H. Mol, Christine L. Mummery, Arie O. Verkerk, Richard P. Davis
Summary: Rare mutations in ion channel genes are the main cause of inherited cardiac arrhythmias, while common genetic variants also play an important role in the clinical heterogeneity observed among mutation carriers. A common SNP, KCNH2-K897T, is associated with QT interval duration, but its effect on disease phenotype in LQT2 patients remains unclear. This study demonstrates that the influence of the common polymorphism KCNH2-K897T on LQT2-causing KCNH2 mutations varies depending on whether it is present in cis or trans orientation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
William A. Agudelo, Sebastian Ramiro Gil-Quinones, Alejandra Fonseca, Alvaro Arenas, Laura Castro, Diana Carolina Sierra-Diaz, Manuel A. Patarroyo, Paul Laissue, Carlos F. Suarez, Rodrigo Cabrera
Summary: Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by prolonged QT interval and T-wave abnormalities, often caused by mutations in genes such as KCNQ1, KCNH2, and SCN5A. This study aimed to investigate the structural impact of compound mutations on potassium channels in severe LQTS phenotypes using molecular dynamic simulations. The findings suggest that mutant channels show moderate changes in energy and mobility, potentially influencing K+ ion flow and differentiating from wild-type channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pediatrics
Thomas Caiffa, Antimo Tessitore, Loira Leoni, Elena Reffo, Daniela Chicco, Biancamaria D'Agata Mottolese, Elisa Rubinato, Giorgia Girotto, Stefania Lenarduzzi, Egidio Barbi, Marco Bobbo, Giovanni Di Salvo
Summary: Physicians should be aware of the rare association between Left ventricular non-compaction (LVNC) and Long QT syndrome (LQTS). This study reports a case of an Italian family with a novel pathogenic KCNH2 variant who presented with clinical features of LVNC and LQTS. The proband and his sister were found to have both LVNC and LQTS, while the father only presented LQTS.
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Huiping Huang, Siyuan Jing, Shaoying Wu, Li Wei, Qian Zhang, Yimin Hua, Yifei Li, Haiyan Yu, Kaiyu Zhou
Summary: This article reports a rare case of fetal Long QT syndrome (LQTS) and high-degree atrioventricular block (AVB) associated with long-term prenatal dexamethasone (DEX) exposure. The study found that genetic screening can help identify channelopathies related to genetic variants and avoid unexpected prenatal exposure of DEX and its potential postnatal complications.
FRONTIERS IN GENETICS
(2022)
Article
Cardiac & Cardiovascular Systems
Krystian Kozek, Yuko Wada, Luca Sala, Isabelle Denjoy, Christian Egly, Matthew J. O'Neill, Takeshi Aiba, Wataru Shimizu, Naomasa Makita, Taisuke Ishikawa, Lia Crotti, Carla Spazzolini, Maria-Christina Kotta, Federica Dagradi, Silvia Castelletti, Matteo Pedrazzini, Massimiliano Gnecchi, Antoine Leenhardt, Joe-Elie Salem, Seiko Ohno, Yi Zuo, Andrew M. Glazer, Jonathan D. Mosley, Dan M. Roden, Bjorn C. Knollmann, Jeffrey D. Blume, Fabrice Extramiana, Peter J. Schwartz, Minoru Horie, Brett M. Kroncke
Summary: Genetic profiling has shown associations between genetic variations and disease, yet pathogenic variants are common in healthy populations. The predictive value of these variants in disease diagnosis needs further investigation.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Li Feng, Jianhua Zhang, ChangHwan Lee, Gina Kim, Fang Liu, Andrew J. Petersen, Evi Lim, Corey L. Anderson, Kate M. Orland, Gail A. Robertson, Lee L. Eckhardt, Craig T. January, Timothy J. Kamp
Summary: This study investigated the pathogenesis of the hERG1-H70R variant in long QT syndrome type 2 using patient-specific iPSC-CMs, revealing a mechanism involving impaired trafficking of hERG1a and maintained expression of hERG1b leading to subunit imbalance and reduced I-Kr.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Na Kyeong Park, Soon-Jung Park, Yun-Gwi Park, Sung-Hwan Moon, Joohan Woo, Hyun Jong Kim, Sung Joon Kim, Seong Woo Choi
Summary: The c.453delC (p.Thr152Profs*14) frameshift mutation in KCNH2 is associated with an elevated risk of Long QT syndrome (LQTS) and fatal arrhythmia. This study found that the mutation leads to the formation of N-terminally truncated hERG channels with diminished expression and reduced current. The use of a hERG activator can ameliorate the abnormalities caused by this mutation.
HUMAN MOLECULAR GENETICS
(2023)