Mutation screening in KCNQ1, HERG, KCNE1, KCNE2 and SCN5A genes in a long QT syndrome family.
BACKGROUND
Long QT syndrome (LQTS), an inherited cardiac arrhythmia, is a disorder of ventricular repolarisation characterised by electrocardiographic abnormalities and the onset of torsades de pointes leading to syncope and sudden death. Genetic polymorphisms in 5 well-characterised cardiac ion channel genes have been identified to be responsible for the disorder. The aim of this study is to identify disease-causing mutations in these candidate genes in a LQTS family.


METHODS
The present study systematically screens the coding region of the LQTS-associated genes (KCNQ1, HERG, KCNE1, KCNE2 and SCN5A) for mutations using DNA sequencing analysis.


RESULTS
The mutational analysis revealed 7 synonymous and 2 non-synonymous polymorphisms in the 5 ion channel genes screened.


CONCLUSIONS
We did not identify any clear identifiable genetic marker causative of LQTS, suggesting the existence of LQTS-associated genes awaiting discovery.
Koo
Seok-Hwee
SH
Department of Pharmacology, National University of Singapore, Singapore.
Teo
Wee-Siong
WS
Ching
Chi-Keong
CK
Chan
Soh-Ha
SH
Lee
Edmund J D
EJ
D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000032:analysis / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000032:analysis / Q000235:genetics*; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011110:Polymorphism, Genetic / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis / Q000235:genetics*; D015222:Sodium Channels / Q000032:analysis / Q000235:genetics*; D015534:Trans-Activators
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels; D015534:Trans-Activators