Change search
ReferencesLink to record
Permanent link

Direct link
Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Show others and affiliations
2012 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, Vol. 12, 95- p.Article in journal (Refereed) Published
Abstract [en]

Background: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort.

Methods: Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umea University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT).

Results: In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death.

Conclusion: In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the RYR2 gene. The mutation panorama is characterised by founder mutations (25%), even so, this cohort increases the amount of known LQTS-associated mutations, as approximately one-third (28%) of the detected mutations were unique.

Place, publisher, year, edition, pages
BioMed Central, 2012. Vol. 12, 95- p.
Keyword [en]
Arrhythmia, Long QT syndrome, Ion-channel, Founder mutation, Variant of unknown significance
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:umu:diva-64060DOI: 10.1186/1471-2261-12-95ISI: 000312312500001OAI: diva2:587722
Available from: 2013-01-15 Created: 2013-01-14 Last updated: 2014-06-17Bibliographically approved

Open Access in DiVA

fulltext(376 kB)134 downloads
File information
File name FULLTEXT01.pdfFile size 376 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Stattin, Eva-LenaBoström, Ida MariaWinbo, AnnikaCederquist, KristinaJonasson, JenniJonsson, Björn-AndersDiamant, Ulla-BrittJensen, Steen MRydberg, AnnikaNorberg, Anna
By organisation
Medical and Clinical GeneticsDepartment of Medical BiosciencesPaediatricsPathologyCardiology
In the same journal
BMC Cardiovascular Disorders
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar
Total: 134 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 125 hits
ReferencesLink to record
Permanent link

Direct link