A candidate locus approach identifies a long QT syndrome gene mutation.
Long QT syndrome is an inherited disorder that results in lengthened cardiac repolarization. It can lead to sudden onset of torsades de pointes, ventricular fibrillation, and death. The authors obtained a family history, performed electrocardiograms, and drew blood for DNA extraction and genotyping from 15 family members representing 4 generations of an affected family. Seven individuals demonstrated prolonged QT intervals. The authors used polymorphic short tandem repeat markers at known LQTS loci, which indicated linkage to chromosome 11p15.5 where the potassium channel, KCNQ1, is encoded. Polymerase chain reaction was used to amplify the coding region of KCNQ1. During survey of the KCNQ1 coding region, a G-to-A transition (G502A) was identified. DNA from all clinically affected but from none of the clinically unaffected family members carried the G-to-A transition. The candidate locus approach allowed an efficient mechanism to uncover the potassium channel mutation causing LQTS in this family.
Beery
Theresa A
TA
College of Nursing, University of Cincinnati, Cincinnati, OH 45221-0038, USA. theresa.beery@uc.edu
Dyment
Macaira
M
Shooner
Kerry
K
Knilans
Timothy K
TK
Benson
D Woodrow
DW
D000293:Adolescent; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008487:Medical History Taking; D018598:Minisatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D040641:Quantitative Trait Loci / Q000235:genetics
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated