Unknown

Dataset Information

0

Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3.


ABSTRACT: Sudden infant death syndrome (SIDS) is one of the leading causes of death during the first year of life. Long QT syndrome (LQTS)-associated mutations may be responsible for 5% to 10% of SIDS cases. We recently established CAV3-encoded caveolin-3 as a novel LQTS-associated gene with mutations producing a gain-of-function, LQT3-like molecular/cellular phenotype.The purpose of this study was to determine the prevalence and functional properties of CAV3 mutations in SIDS.Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, postmortem genetic testing of CAV3 was performed on genomic DNA isolated from frozen necropsy tissue on a population-based cohort of unrelated cases of SIDS (N = 134, 57 females, average age = 2.7 months). CAV3 mutations were engineered using site-directed mutagenesis and heterologously expressed in HEK293 cell lines stably expressing the SCN5A-encoded cardiac sodium channel.Overall, three distinct CAV3 mutations (V14L, T78M, and L79R) were identified in three of 50 black infants (6-month-old male, 2-month-old female, and 8 month-old female), whereas no mutations were detected in 83 white infants (P <.05). CAV3 mutations were more likely in decedents 6 months or older (2/12) than in infants who died before 6 months (1/124, P = .02). Voltage clamp studies showed that all three CAV3 mutations caused a significant fivefold increase in late sodium current compared with controls.This study provides the first molecular and functional evidence implicating CAV3 as a pathogenic basis of SIDS. The LQT3-like phenotype of increased late sodium current supports an arrhythmogenic mechanism for some cases of SIDS.

SUBMITTER: Cronk LB 

PROVIDER: S-EPMC2836535 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3.

Cronk Lisa B LB   Ye Bin B   Kaku Toshihiko T   Tester David J DJ   Vatta Matteo M   Makielski Jonathan C JC   Ackerman Michael J MJ  

Heart rhythm 20061206 2


<h4>Background</h4>Sudden infant death syndrome (SIDS) is one of the leading causes of death during the first year of life. Long QT syndrome (LQTS)-associated mutations may be responsible for 5% to 10% of SIDS cases. We recently established CAV3-encoded caveolin-3 as a novel LQTS-associated gene with mutations producing a gain-of-function, LQT3-like molecular/cellular phenotype.<h4>Objective</h4>The purpose of this study was to determine the prevalence and functional properties of CAV3 mutations  ...[more]

Similar Datasets

| S-EPMC2810855 | biostudies-literature
| S-EPMC2909680 | biostudies-literature
| S-EPMC3720711 | biostudies-literature
| S-EPMC5317164 | biostudies-literature
| S-EPMC6858687 | biostudies-literature
| S-EPMC1359045 | biostudies-literature
| S-EPMC7894824 | biostudies-literature
| S-EPMC4444798 | biostudies-literature
| S-EPMC8183887 | biostudies-literature
2024-01-04 | GSE245891 | GEO