Channelpedia

PubMed 24021552


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv11.1 , Kv7.1 , Kv8.2



Title: The Role of CAV3 in Long QT Syndrome: Clinical and Functional Assessment of a Caveolin-3/Kv11.1 Double Heterozygote Versus Caveolin-3 Single Heterozygote.

Authors: Paula L Hedley, Jørgen K Kanters, Maja Dembic, Thomas Jespersen, Lasse Skibsbye, Frederik H Aidt, Ole Eschen, Claus Graff, Elijah R Behr, Sarah Schlamowitz, Valerie Corfield, William J McKenna, Michael Christiansen

Journal, date & volume: Circ Cardiovasc Genet, 2013 Sep 10 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24021552


Abstract
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.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.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.