Abstract
BackgroundLong QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A.MethodsWe describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2.ResultsTwenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 “unrelated” families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000.ConclusionThe genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.
Highlights
Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death
Patients The patients were 70 Danish LQTS probands from unrelated families where mutation screening in the five LQTS associated genes KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A had led to the identification of a disease-causing mutation
A large proportion of patients were examined for large deletions in KCNQ1, KCNH2, KCNE1, KCNE2 and a small part of SCN5A by multiplex-ligation-dependent amplification (MLPA) using the SALSA MLPA P114 kit (MRC-Holland, Amsterdam, The Netherlands)
Summary
Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. Long QT syndrome (LQTS) is a genetic disease of the cardiac electrical system which presents clinically with palpitations, syncope and sudden death [1,2]. More than 700 disease-causing mutations have been found in 13 genes [1,2,3] and the total number of mutations is probably larger [4] All these genes are directly or indirectly involved in the execution of the cardiac action potential (AP) [2]. The genetic diagnostic work is centred in five University cardiology clinics and patients are offered a five-gene screen of the most frequently affected genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2. We compare the distribution of mutations with that found in other population studies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
