Ninth gene for Brugada syndrome (BRGDA9)

Ninth gene for Brugada syndrome (BRGDA9)

The eight previously known Brugada syndrome susceptibility genes are [three sodium channel (SCN) genes, two potassium channel(KCN) genes, two calcium channel (CACN) genes and one glycerol-3-phosphate dehydrogenase(GPD) 1-like gene]:
BRGDA1: SCN5A
BRGDA2: GPD1L
BRGDA3: CACNA1C
BRGDA4: CACNB2
BRGDA5: SCN1B
BRGDA6: KCNE3
BRGDA7: SCN3B
BRGDA8: KCNJ8
BRGDA9: KCND3

John R Giudicessi, Dan Ye, David J Tester, Lia Crotti, Alessandra Mugione, Vladislav V Nesterenko, Richard M Albertson, Charles Antzelevitch, Peter J Schwartz and Michael J Ackerman [1] have identified the ninth gene for Brugada syndrome mutation in the KCND3-encoded Kv4.3 (Ito), which is a missense mutation. These mutations (Kv4.3-L450F and Kv4.3-G600R) had a gain-of-function phenotype which increased the peak Ito (transient outward) current density. This (KCND3 mutation) is the ninth gene for Brugada syndrome to be identified and has been designated BRGDA9 by Online Mendelian Inheritance in Man (OMIM) database. The authors also demonstrated a stable loss of the action potential dome due to the increased Ito maximal conductance with these mutations. They noted the possibility of lethal arrhythmia with this mutation precipitated by enhanced Ito current gradient within the right ventricle where KCND3 expression is highest.

Reference

  1. John R Giudicessi, Dan Ye, David J Tester, Lia Crotti, Alessandra Mugione, Vladislav V Nesterenko, Richard M Albertson, Charles Antzelevitch, Peter J Schwartz, Michael J Ackerman. Transient outward current (Ito) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm. 2011 Jul;8(7):1024-32.