The role of CAV3 in long QT : clinical and functional assessment of a caveolin-3/Kc11.1 compound heterozygote

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dc.contributor.authorHedley, Paula L.en_ZA
dc.contributor.authorKanters, Jorgen K.en_ZA
dc.contributor.authorDembic, Majaen_ZA
dc.contributor.authorJesperson, Thomasen_ZA
dc.contributor.authorSkibsbye, Lasseen_ZA
dc.contributor.authorAidt, Frederik H.en_ZA
dc.contributor.authorEschen, Oleen_ZA
dc.contributor.authorGraff, Clausen_ZA
dc.contributor.authorBehr, Elijah R.en_ZA
dc.contributor.authorSchlamowitz, Sarahen_ZA
dc.contributor.authorCorfield, Valerie A.en_ZA
dc.contributor.authorMcKenna, Willim J.en_ZA
dc.contributor.authorChristiansen, Michaelen_ZA
dc.date.accessioned2014-07-07T12:18:43Z
dc.date.available2014-07-07T12:18:43Z
dc.date.issued2013
dc.descriptionCITATION: Hedley, P. L. et al. 2013. The role of CAV3 in long QT : clinical and functional assessment of a caveolin-3/Kc11.1 compound heterozygote. Circulation: Cardiovascular Genetics, 6:452-461, doi:10.1161/CIRCGENETICS.113.000137.
dc.descriptionThe original publication is available at https://www.ahajournals.org
dc.description.abstractBackground— Mutations in CAV3, coding for caveolin-3, the major constituent scaffolding protein of cardiac caveolae, have been associated with skeletal muscle disease, cardiomyopathy, and most recently long–QT syndrome (LQTS) and sudden infant death syndrome. We examined the occurrence of CAV3 mutations in a large cohort of patients with LQTS. Methods and Results— Probands with LQTS (n=167) were screened for mutations in CAV3 using direct DNA sequencing. A single proband (0.6%) was found to be a heterozygous carrier of a previously described missense mutation, caveolin-3:p.T78M. The proband was also a heterozygous carrier of the trafficking-deficient Kv11.1:p.I400N mutation. The caveolin-3:p.T78M mutation was found isolated in 3 family members, none of whom had a prolonged QTc interval. Coimmunoprecipitations of caveolin-3 and the voltage-gated potassium channel subunit (Kv11.1) were performed, and the electrophysiological classification of the Kv11.1 mutant was carried out by patch-clamp technique in human embryonic kidney 293 cells. Furthermore, the T-wave morphology was assessed in mutation carriers, double mutation carriers, and nonmutation carriers by applying a morphology combination score. The morphology combination score was normal for isolated caveolin-3:p.T78M carriers and of LQT2 type in double heterozygotes. Conclusions— Mutations in CAV3 are rare in LQTS. Furthermore, caveolin-3:p.T78M did not exhibit a LQTS phenotype. Because no association has ever been found between LQTS and isolated CAV3 mutations, we suggest that LQTS9 is considered a provisional entity.
dc.description.urihttps://www.ahajournals.org/doi/10.1161/CIRCGENETICS.113.000137
dc.description.versionPublisher's version
dc.format.extent10 pages
dc.identifier.citationHedley, P. L. et al. 2013. The role of CAV3 in long QT : clinical and functional assessment of a caveolin-3/Kc11.1 compound heterozygote. Circulation: Cardiovascular Genetics, 6:452-461, doi:10.1161/CIRCGENETICS.113.000137.
dc.identifier.issn1941-3084 (online)
dc.identifier.otherdoi:10.1161/CIRCGENETICS.113.000137
dc.identifier.urihttp://hdl.handle.net/10019.1/93413
dc.language.isoen
dc.publisherAmerican Heart Association
dc.rights.holderAmerican Heart Association
dc.subjectLong QT syndromeen_ZA
dc.subjectCAV3en_ZA
dc.titleThe role of CAV3 in long QT : clinical and functional assessment of a caveolin-3/Kc11.1 compound heterozygoteen_ZA
dc.typeArticle
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