Does KCNE5 play a role in long QT syndrome?
BACKGROUND
Long QT syndrome [LQTS] is a congenital cardiac disease characterised by prolonged QTC-time, syncopes and sudden cardiac death. LQTS is caused by mutations in genes coding for ion channels involved in the action potential. KCNE5 codes for a novel beta-subunit of the ion channel conducting the delayed rectifier repolarizing current IKs. As KCNE5 is expressed in the human heart and suppresses the IKs current in heterologous systems, it is a candidate gene that may be mutated in LQTS families where no causative mutations in known LQTS associated genes have been found. We examined whether this was the case.


METHODS
Genomic DNA from LQTS patients [n=88] and normal controls [n=90] was screened for mutations in KCNE5 by endonuclease-enhanced single strand conformation polymorphism analysis [EE-SSCP], and DNA sequencing of aberrant conformers. Mutations in other LQTS associated ion channels were excluded by SSCP.


RESULTS
No mutations were found in the coding region of the KCNE5 gene in LQTS patients. One polymorphism, a T-to-C transition at nucleotide 97, causing an amino acid polymorphism P33S, was present in 16 persons, nine heterozygotes and seven homozygotes. The T-allele frequency was 0.13 in LQTS patients and 0.10 in controls.
Hofman-Bang
Jacob
J
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
Jespersen
Thomas
T
Grunnet
Morten
M
Larsen
Lars Allan
LA
Andersen
Paal Skytt
PS
Kanters
Jørgen Kim
JK
Kjeldsen
Keld
K
Christiansen
Michael
M
D000200:Action Potentials / Q000502:physiology; D000595:Amino Acid Sequence; D019295:Computational Biology; D004252:DNA Mutational Analysis; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C502068:KCNE5 protein, human; D024642:Potassium Channels, Voltage-Gated