Objective
The long QT syndrome (LQTS) is a known cause of sudden death in young individuals. In Scandinavia, LQT founder mutations explain 73% of LQTS in Finland, while in Norway the mutational spectrum is diverse without founder mutations. This study investigates the occurrence of the Y111C-KCNQ1 mutation in the Swedish population, where the LQTS mutational spectrum is previously unknown.
Methods and Results
In Sweden we have, so far, identified 122 carriers of a LQT1 mutation (Y111C-KCNQ1) in 27 index families. Presently, Y111C constitutes almost a third of all identified LQTS mutations in probands analyzed at the Department of Clinical Genetics, Umeå University Hospital, Sweden.
The founder mutation concept is based on genealogical, geographical and genetic evidence. A common founder for 9 of the families, a woman who married twice, born in 1694 in northern Sweden has been identified. Interconnections between several other index families are being established. Ancestors of 19 probands originate from the same geographic region.
In March 2009, investigations to determine the age of the mutation is planned, and analysis of microsatellite markers will provide formal evidence as to whether the Y111C mutation is the first Swedish LQT founder mutation.
Conclusions
The Y111C mutation, the first Swedish LQT founder mutation by genealogical and geographical evidence, is a substantial cause of LQTS in Sweden. Genetic analysis will conclusively reveal whether the occurrence of the Y111C mutation in the Swedish population is “hot spot” or a founder effect.