[DNA-based diagnostics of long QT syndrome].
BACKGROUND
Long QT syndrome is characterised by inherited long QT interval on the ECG and increased risk for syncope and sudden death caused by arrhythmias. For Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome DNA based diagnostics are available.


METHODS
This paper is a summary of our experience with DNA-based diagnostics of LQTS since the autumn of 2003. The diagnostic analyses are performed by sequencing the exons of five genes, KCNQ1, HERG, SCN5A, minK and MiRP1.


CONCLUSIONS
As of mid-January 2005, 56 probands with long QT syndrome have been referred for genetic testing. We have identified an underlying mutation in 64% of the patients. Mutations in the KCNQ1 gene are most frequent in Norwegian long QT syndrome patients, as 61% of the patients have their mutation in this gene. The detection of a mutation in the probands has led to genetic testing of 215 relatives; 99 out of these are heterozygous for the mutation present in the family. Heterozygous patients have been referred to a cardiologist. Of the 43 that have been referred to follow up at the department of cardiology at Rikshospitalet, 35 have started treatment with beta blockers to reduce the risk of arrhythmias. Thus, DNA-based diagnostics has clinical significance leading to prophylactic treatment of long QT syndrome patients. Compared to evaluation of ECG, which is negative in 30% of mutation carriers, the sensitivity of DNA-based diagnostics of relatives of probands with a known mutation, is close to 1.
Berge
Knut Erik
KE
Avdeling for medisinsk genetikk, Rikshospitalet, 0027 Oslo. knut.erik.berge@rikshospitalet.no
Haugaa
Kristina Hermann
KH
Anfinsen
Ole-Gunnar
OG
Früh
Andreas
A
Hallerud
Maria
M
Jonsrud
Christoffer
C
Øyen
Nina
N
Gjesdal
Knut
K
Amlie
Jan P
JP
Leren
Trond P
TP
D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics*
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489619:KCNE2 protein, human; C000606913:KCNH2 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels; C497353:MINK1 protein, human; D017346:Protein Serine-Threonine Kinases