E. Schulzebahr et al., MOLECULAR ANALYSIS AT THE HARVEY RAS-1 GENE IN PATIENTS WITH LONG QT SYNDROME, Journal of molecular medicine, 73(11), 1995, pp. 565-569
Citations number
32
Categorie Soggetti
Medical Laboratory Technology","Genetics & Heredity
Patients with long QT syndrome (LQTS; MIM 192\500) frequently suffer f
rom syncope and are threatened by sudden cardiac death due to ventricu
lar arrhythmias, typically of the torsade de pointes type. Initial pro
gress in revealing the molecular basis of the disease was made by the
observation of genetic linkage of the disease locus to the Harvey Ras-
1 gene (HRAS 1) on chromosome 11p15.5. More recently loci on chromosom
es 3, 4, and 7 have also been found to be linked to LQTS, thus demonst
rating heterogeneity in the causes for this disease. The present study
performed sequence analysis on the HRAS 1 gene in patients with conge
nital and acquired LQTS to determine the frequency of HRAS 1 mutations
in patients with this disease. In neither group were no mutations ide
ntified in the coding regions or in the splice donor and acceptor site
s. Alleles characterized by a T to C transition in exon 1 and an inser
tion/deletion polymorphism upstream of exon 1 showed no significant di
fference in their frequencies between LQTS patients and normal control
s. No quantitative influence of the such characterized genotypes on th
e QT duration was observed. These results demonstrate that structural
mutations in the HRAS 1 gene are not a frequent cause of LQTS. Also, s
ince there was no association of different alleles at the HRAS 1 locus
with changes in QT duration, it appears unlikely that this gene is a
major contributor to this disease.