umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. (Heart Centre)
Show others and affiliations
2014 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 14, 22- p.Article in journal (Refereed) Published
Abstract [en]

Background: The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome-JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p. R518X mutation. Methods: The study included 19 Swedish p. R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software). Results: Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 +/- 61 ms vs. 462 +/- 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%). A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p. R518X heterozygotes was suggested (similar to 1: 2000-4000). Conclusions: R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

Place, publisher, year, edition, pages
BioMed Central, 2014. Vol. 14, 22- p.
Keyword [en]
Long QT Syndrome, Genotype-phenotype correlations, Clinical phenotype, Founder mutation, Mutation age, Prevalence estimate
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-88970DOI: 10.1186/1471-2261-14-22ISI: 000334534000001OAI: oai:DiVA.org:umu-88970DiVA: diva2:719590
Available from: 2014-05-26 Created: 2014-05-19 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

fulltext(1118 kB)141 downloads
File information
File name FULLTEXT01.pdfFile size 1118 kBChecksum SHA-512
1eab5148686d2ab4f995293c73fec52fe1ea35aa7844be9738496c3b9adfea6d7acf7b8306d1f22d99cecca71ccb0ab363a5f1c83e2aff2c3540a273bb77a501
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Winbo, AnnikaStattin, Eva-LenaDiamant, Ulla-BrittJensen, Steen M.Rydberg, Annika

Search in DiVA

By author/editor
Winbo, AnnikaStattin, Eva-LenaNordin, CharlotteDiamant, Ulla-BrittPersson, JohanJensen, Steen M.Rydberg, Annika
By organisation
PaediatricsMedical and Clinical GeneticsCardiology
In the same journal
BMC Cardiovascular Disorders
Pediatrics

Search outside of DiVA

GoogleGoogle Scholar
Total: 141 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

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 235 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf