Abstract
Congenital long QT syndrome (LQTS) is a genetic disease that predisposes affected individuals to arrhythmias, syncope, and sudden death. Mutations in several ion channel genes have been discovered in different families with LQTS: KCNQ1 (KVLQT1, LQT1), KCNH2 (HERG, LQT2), SCN5A (LQT3), KCNE1 (minK, LQT5), and KCNE2 (MiRP1, LQT6). Previously, the P448R-KVLQT1 missense mutation has been reported as an LQT1-causing mutation. In this report, we demonstrate the presence of the P448R polymorphism in two, unrelated Chinese LQTS families. Although absent from 500 reference alleles derived from 150 white and 100 African-American subjects, P448R was present in 14% of healthy Chinese volunteers. Given the inconsistencies between the genotype (LQT1) and clinical phenotype (LQT2) in our two LQTS families, together with the finding that the P448R appears to be a common, ethnic-specific polymorphism, mutational analysis was extended to the other LQTS-causing genes resulting in the identification of distinct HERG missense mutations in each of these two families. Heterologous expression of P448R-KVLQT1 yielded normal, wild-type (WT) currents. In contrast, the two unique HERG mutations resulted in dominant-negative suppression of the WT HERG chan...Continue Reading
Citations
Nov 29, 2013·Journal of Human Genetics·Sayako KameiHideki Asamura
Jan 11, 2013·ISRN Cardiology·Ronald Wilders
Oct 4, 2006·Cardiology·Zhiyu ZengJielin Pu
Feb 21, 2006·British Journal of Clinical Pharmacology·Seok Hwee KooEdmund Jon Deoon Lee
Feb 26, 2015·The Journal of General Physiology·Wenying WangEbenezer N Yamoah
Feb 24, 2015·Frontiers in Cellular Neuroscience·Atefeh Mousavi NikHyo Jeong Kim
Apr 6, 2012·PloS One·Xing-dong ChenXiao-feng Wang
May 19, 2006·Expert Review of Molecular Diagnostics·Chi-Keong Ching, Ene-choo Tan
Sep 23, 2014·The Journal of Allergy and Clinical Immunology·Heleen D de KoningAnna Simon
Apr 17, 2008·British Journal of Pharmacology·Y H WangY F Xu
Aug 21, 2008·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Judy F LiuMark L Andrews
Nov 8, 2005·Molecular Diagnosis : a Journal Devoted to the Understanding of Human Disease Through the Clinical Application of Molecular Biology·G Michael Vincent, Li Zhang
Sep 27, 2005·Physiological Reviews·Jeanne M Nerbonne, Robert S Kass
Jan 2, 2009·Scandinavian Cardiovascular Journal : SCJ·Søren LundeErik Sloth
Oct 15, 2013·Scandinavian Journal of Psychology·Allan B I Bernardo
Jul 5, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katja SteinkeGuiscard Seebohm
Jun 10, 2017·BMC Medical Genetics·Motoi NishimuraFumio Nomura
Jun 16, 2018·Frontiers in Pharmacology·Tao JinZhao Zhang
May 30, 2020·International Journal of Cardiology·Nejat MahdiehBahareh Rabbani