Analysis of candidate genes for genotypic diagnosis in the long QT syndrome.
Patients with the long QT syndrome (LQTS) suffer from cardiac arrhythmias that can lead to abrupt loss of consciousness and sudden death, already in young individuals. Thus, an early diagnosis of LQTS is essential for patients and their family members. So far, six genes (KCNQ1, HERG, SCN5A, ANK2, KCNE1, KCNE2) have been demonstrated to be involved in the development of LQTS. Since this syndrome is genetically heterogeneous and large-sized families are often not available for linkage analysis, alternative tools are required for a genetic diagnosis. To investigate genes with numerous exons, like KCNQ1, HERG, SCN5A and ANK2, segregation analysis of a Polish Romano-Ward family with eight members was performed as a reliable method faster than linkage analysis or direct sequencing. To test these four LQT loci, an appropriate selection of microsatellite markers covering different chromosomal regions was applied. Furthermore, two small genes KCNE1 and KCNE2 (at the LQT5 and LQT6 loci), and the SGK1 gene (encoding a kinase regulating KCNE1 and SCN5A channels) were sequenced. All six LQT loci and the SGK1 gene were excluded by these analyses, thus a different pathogenic mechanism of LQT syndromes can be presumed.
Haack
Birgit
B
Division of Molecular Genetics, University of Tübingen, Wilhelmstr. 27, 72074 Tübingen, Germany.
Kupka
Susan
S
Ebauer
Margret
M
Siemiatkowska
Anna
A
Pfister
Markus
M
Kwiatkowska
Joanna
J
Ereciński
Jan
J
Limon
Janusz
J
Ochman
Karolina
K
Blin
Nikolaus
N
D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree
D017931:DNA Primers