Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome.
BACKGROUND
Long QT syndrome (LQTS) is a hereditary cardiac arrhythmogenic disorder characterized by prolongation of the QT interval in the electrocardiogram, torsades de pointes arrhythmia, and syncopes and sudden death. LQTS is caused by mutations in ion channel genes. However, only in half of the families is it possible to identify mutations in one of the seven known LQTS genes, why further genetic heterogeneity is expected. The genes KCND2 and KCND3, encoding the alpha-subunits of the voltage-gated potassium channels Kv4.2 and Kv4.3 conducting the fast transient outward current (I(TO,f)) of the cardiac action potential (AP) in the myocardium, have been associated with prolongation of AP duration and QT prolongation in murine models.


METHODS
KCND2 and KCND3 were examined for mutations using single-strand conformation polymorphism (SSCP) analysis in 43 unrelated LQTS patients, where mutations in the coding regions of known LQTS genes had been excluded.


RESULTS
Seven single nucleotide polymorphismsm (SNPs) were found, two exonic SNPs in KCND2 and three exonic and two intronic in KCND3. None of the five exonic SNPs had coding effect. All seven SNPs are considered normal variants.


CONCLUSIONS
The data suggest that mutations in KCND2 and KCND3 are not a frequent cause of long QT syndrome.
Frank-Hansen
Rune
R
Department of Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark.
Larsen
Lars Allan
LA
Andersen
Paal
P
Jespersgaard
Cathrine
C
Christiansen
Michael
M
D000200:Action Potentials / Q000502:physiology; D000483:Alleles; D000818:Animals; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D006321:Heart / Q000502:physiology*; D006801:Humans; D007438:Introns / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels
C497018:KCND2 protein, human; C497021:KCND3 protein, human; C497022:Kcnd3 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels