1 / 17

Long QT Syndrome Type 3 (LQT 3) Mutations in SCN5A (Na+ Channel, I Na ) BME 301

Long QT Syndrome Type 3 (LQT 3) Mutations in SCN5A (Na+ Channel, I Na ) BME 301 Silvia Castillo, Qaiyim Cheeseborough, Victoria Reyes, Kin Siu. Introduction to LQT. Disorder caused by mutations in cardiac ion channels Most associated with K+ channels. Symptoms. Fainting (syncope)

urban
Télécharger la présentation

Long QT Syndrome Type 3 (LQT 3) Mutations in SCN5A (Na+ Channel, I Na ) BME 301

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Long QT Syndrome Type 3 (LQT 3) Mutations in SCN5A (Na+ Channel, INa) BME 301 Silvia Castillo, Qaiyim Cheeseborough, Victoria Reyes, Kin Siu

  2. Introduction to LQT • Disorder caused by mutations in cardiac ion channels • Most associated with K+ channels

  3. Symptoms • Fainting (syncope) • Seizures • Cardiac arrest • Sudden Death

  4. Diagnosis • Diagnosis is preformed by analyzing the EKG readings in response to the T – wave. • A autopsy may be conducted of LQT 3 syndrome through examining the SCN5A gene Normal EKG Long QT syndrome

  5. Genetic Picture of SCN5A • Located on human 3p21 chromosome • Encodes alpha subunit of cardiac sodium channel protein

  6. Specific Mutations • 17 known mutations, 14 are single nucleotide

  7. Physical Characteristics • 2016 amino acids • Sequence – 4 internal repeats, with 5 hydrophobic segments and 1 positively charged segment each

  8. Function • Forms voltage-dependent, sodium selective channel • Positively charged segments most likely the voltage sensors • Responsible for initial upstroke in an action potential

  9. Protein Mechanism for Disorder • Poorly understood • III-IV linker region as blocking particle • C-Terminus as a docking station • Mutations at these regions can cause failure in inactivation

  10. Mechanism for Disorder • Fraction of Na+ channels fail to inactivate • Cause sustained Na+ ion influx • Leads to longer QT-intervals in an electrocardiogram

  11. Drug Treatment - 1 • Lidocaine • Most commonly used • Inhibits the influx of sodium

  12. Drug Treatment - 2 • Mexiletine • Orally administered • Mechanism similar to Lidocaine

  13. Drug Treatment - 3 • Flecainide • Mechanism similar to Lidocaine

  14. Risk Factors • History of syncope • Duration of episode and QT interval • Congenital deafness • Male children • Female pregnancy cardiac events are common

  15. Statistics • 8% of all LQT carriers have SCN5A mutations • Case study – found LQT-3 more lethal • Onset: 50% by 12 years; 90% by 40 years

  16. References • Neuromuscular Disease Center. ION CHANNELS, TRANSMITTERS, RECEPTORS & DISEASE. 10 Feb 2000. < http://www.neuro.wustl.edu/neuromuscular/mother/chan.html>

  17. ANY QUESTIONS ???

More Related