CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 6, July 2013
AFRICA
235
of cLQTS cases globally; gene rearrangements could account for
a portion of these.
Furthermore, we only screened five of the 13 known LQTS-
causing genes. However, the small sample size limits the
possibility of identifying variants in genes that are rarely
associated with cLQTS. These genes typically exhibit a
prevalence of
<
1% of the LQTS population.
4
Conclusion
Genetic screening of five frequently implicated cLQTS causative
genes in a predominantly white South African cLQTS cohort
led to the identification of a disease-causing mutation in
77% of examined cases. The previously described founder
mutation, p.A341V, is responsible for cLQTS in 52% of these
probands, meaning that the extended screening increases the
detection by 29% points. Furthermore, the frequency of double
heterozygozity in South Africa is similar to the frequency seen
in other populations.
54
Therefore, 8.5% of the founder mutation-
carrying families had members that were double heterozygotes.
These findings emphasise the importance of performing a
comprehensive genetic screening when doing genetic work up,
even in a population with a large founder effect. Despite the
impressive diagnostic rate found here, it should be remembered
that, using current techniques, it is not yet possible to establish a
genetic diagnosis in many (23%) cLQTS families. In these cases,
and wherever the clinical picture is complex, it is of paramount
importance to realise that LQTS is a clinical condition requiring
clinical management, irrespective of the genetic aetiology.
We thank Ina le Roux, Christine Bugay Valdez, Dennis Dion Petersen
and Karina Liebmann Madsen for their excellent technical assistance. We
acknowledge the financial support of the South African National Research
Foundation, the Harry and Doris Crossley Foundation and the Danish
Strategic Research Foundation.
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