None of the authors declare a conflict of interest.
LQTS in Northern BC: homozygosity for KCNQ1 V205M presents with a more severe cardiac phenotype but with minimal impact on auditory function
Article first published online: 30 JUL 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
LQTS in Northern BC: homozygosity for KCNQ1 V205M presents with a more severe cardiac phenotype but with minimal impact on auditory function., , , , , , , .
- Article first published online: 30 JUL 2013
- Accepted manuscript online: 11 JUL 2013 07:54AM EST
- Manuscript Accepted: 8 JUL 2013
- Manuscript Revised: 3 JUL 2013
- Manuscript Received: 5 JUN 2013
- Canadian Institutes of Health Research. Grant Number: 81197
- hearing loss;
- long QT syndrome;
Long QT syndrome (LQTS), a rare congenital cardiac condition associated with life-threatening ventricular arrhythmias is characterized by a prolonged QT interval on electrocardiograph corrected for heart rate [corrected QT (QTc)]. LQTS has been historically categorized into the autosomal dominant Romano–Ward syndrome (RWS) and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS). JLNS is associated with prelingual sensorineural deafness. Both types of LQTS can be caused by mutations in channel genes (e.g. KCNQ1) responsible for potassium homeostasis in cardiac myocytes and cochlea. Autosomal dominant mutations often cause the RWS phenotype and homozygous or compound heterozygous mutations contribute to JLNS. Two First Nations communities in northern British Columbia are affected disproportionately with LQTS largely due to the V205M mutation in KCNQ1, however, the pathology and phenotypic expression for those V205M homozygous has been unknown. Here, we show that four V205M homozygous individuals have a significantly higher ‘peak’ QTc, and a more severe cardiac phenotype compared with 41 V205M heterozygous carriers and 57 first to third degree relatives without mutations. Given the lack of prelingual deafness the homozygous V205M LQTS patients present with a phenotype more typical of RWS than JLNS.