Expression of a Common LQT1 Mutation in Five Apparently Unrelated Families in a Regional Inherited Arrhythmia Clinic


  • The study was supported by the Heart and Stroke Foundation of Ontario (NA3397). Dr. Krahn is a Career Investigator of the Heart and Stroke Foundation of Ontario.

  • Dr. Salisbury is an employee of Clinical Data, Inc. and owns stock and options in the company. No other conflicts of interest were declared.

Address for correspondence: Dr. Andrew Krahn, M.D., Arrhythmia Service, London Health Sciences Centre, 339 Windermere Road, London, Ontario, Canada N6A 5A5. Fax: 1-519-663-3782; E-mail:


Expression of a Common LQT1 Mutation. Background: The Inherited Arrhythmia Clinic at the University of Western Ontario services a catchment area of 1.5 million people and follows families with inherited arrhythmia syndromes.

Methods: Patients referred for evaluation of long-QT Syndrome (LQTS) are evaluated with resting and standing ECGs, and treadmill exercise testing. Patients with findings consistent with LQTS are offered comprehensive genetic testing with screening of all first-degree relatives of genotype-positive patients.

Results: Among 31 probands with disease-causing LQTS mutations, 5 probands from apparently unrelated families of Irish descent were found to have an identical disease causing transmembrane mutation in KCNQ1 (Leu266Pro). Systematic screening of 33 first-degree relatives of genotype-positive individuals detected 15 unaffected and 18 asymptomatic affected family members. Symptoms in 6 patients occurred later in life than reported LQT1 populations (61 ± 18 years, range 44–89). In this cohort, several family members presented with cardiac arrest during acute myocardial ischemia (n = 2), sudden death, unexplained drowning, and torsade de pointes during exercise testing. There was no identifiable common relative for this cohort after pedigree construction of the previous 4–7 generations. Affected patients had mild QT prolongation at rest with dramatic QT prolongation with exercise.

Conclusions: Genetic testing in this LQTS population suggests a common KCNQ1 Leu266Pro founder effect, with the descendants clustering in our geographical region even though no common relative has been identified. The observations highlight the utility of genotypic and phenotypic correlation and a specialized clinic. (J Cardiovasc Electrophysiol, Vol. 21, pp. 296–300, March 2010)