SwePub
Sök i LIBRIS databas

  Extended search

id:"swepub:oai:DiVA.org:umu-57723"
 

Search: id:"swepub:oai:DiVA.org:umu-57723" > The Swedish long QT...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Winbo, Annika,1978-Umeå universitet,Pediatrik (author)

The Swedish long QT syndrome R518X/KCNQ1 founder population- origin and clinical phenotype : phenotypic variability partly explained by gender-specific effects of sequence variants in the NOS1AP gene

  • BookEnglish

Publisher, publication year, extent ...

  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-57723
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-57723URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:vet swepub-contenttype
  • Subject category:ovr swepub-publicationtype

Notes

  • Manuskriptets titel i avhandlingen: Phenotype and origin of the Swedish long QT syndrome R518X/KCNQ1 founder population - phenotypic variability partly explained by gender-specific effects of genetic modifiers.
  • Background: Genetic modifiers have been proposed to explain phenotypic variability in the long QT syndrome (LQTS). We investigate the origin and phenotype of the worldwide common R518X/KCNQ1 mutation in Sweden, as well as possible associations between p.R518X-LQTS phenotype and previously reported modifying sequence variants in the NOS1AP, KCNH2, KCNE1, SCN5A and KCNQ1(3’UTR) genes. Methods and Results: We identified 19 p.R518X families (101 mutation-carriers, whereof 15 Jervell and Lange-Nielsen (JLNS) cases and 86 LQTS cases). Analyses of microsatellite markers, genealogy and mutation age (ESTIAGE) identified a common northern origin ~700 years ago for 17/19 families and a high prevalence of Swedish p.R518X heterozygotes was suggested (DMLE). Clinical phenotype ranged from severe in JLNS to relatively 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%).In p.R518X-LQTS males, two NOS1AP variants rs12143842 and rs16847548 were associated with a 29 ms QT prolongation (p=0.004), explaining 27% of QTc variability.Three derived 3’UTR-KCNQ1 variants, previously shown to suppress gene expression in an allele-specific manner, were found to segregate with the founder mutation.Conclusion: The R518X/KCNQ1 mutation is a Swedish founder mutation presenting with an expectedly severe phenotype in JLNS and an unusually mild phenotype in LQTS, although intra-familial variability remained. Gender-specific effects of NOS1AP sequence variants explained over a fourth of QTc variance in p.R518X-LQTS males, warranting further studies. Repressive 3’UTR-KCNQ1 sequence variants segregating within the founder haplotype could possibly contribute to its relative benignancy.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Stattin, Eva-LenaUmeå universitet,Medicinsk och klinisk genetik (author)
  • Norberg, AnnaUmeå universitet,Medicinsk och klinisk genetik (author)
  • Nordin, CharlotteUmeå universitet,Pediatrik (author)
  • Diamant, Ulla-BrittUmeå universitet,Klinisk fysiologi(Swepub:umu)uldi0001 (author)
  • Persson, JohanUmeå universitet,Pediatrik (author)
  • Jensen, Steen MUmeå universitet,Medicin(Swepub:umu)stje0001 (author)
  • Rydberg, AnnikaUmeå universitet,Pediatrik(Swepub:umu)anry0014 (author)
  • Umeå universitetPediatrik (creator_code:org_t)

Internet link

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view