Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death

Background: sudden cardiac death (scd) is the clinical outcome of a lethal arrhythmia that can develop on the background of unrecognized channelopathies or cardiomyopathies. several susceptibility genes have been identified for the congenital forms of these cardiac diseases,including caveolin-3 (cav-3) gene. in the heart cav-3 is the main component of caveolae,plasma membrane domains that regulate multiple cellular processes highly relevant for cardiac excitability,such as trafficking,calcium homeostasis,signal transduction and cellular response to injury. here we characterized a new putative cav-3 variant,cav-3 v82i,found in a patient with scd. results: in heterologous systems cav-3 v82i was expressed at significantly higher level than cav-3 wt and accumulated within the cells. cells expressing cav-3 v82i exhibited a decreased activation of extracellular-signal-regulated kinases (erks) and were more vulnerable to sub-lethal osmotic stress. conclusion: considering that abnormal loss of myocytes can play a mechanistic role in lethal cardiac diseases,we suggest that the detrimental effect of cav-3 v82i variant on cell viability may participate in determining the susceptibility to cardiac death. © 2014 lariccia et al.; licensee biomed central ltd.