title: The genetic basis of Brugada syndrome: a mutation update.
abstract: Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the alpha-subunit of the Na(v)1.5 sodium ion channel conducting the depolarizing I(Na) current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the alpha-subunit of the Ca(v)1.2 ion channel conducting the depolarizing I(L,Ca) current; CACNB2, which encodes the stimulating beta2-subunit of the Ca(v)1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes beta-subunits of the Na(v)1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory beta-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I(to) current. BrS exhibits variable expressivity, reduced penetrance, and "mixed phenotypes," where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hedley
authors.forename: Poul
authors.initials: P
authors.lastname: Jørgensen
authors.forename: Sarah
authors.initials: S
authors.lastname: Schlamowitz
authors.forename: Johanna
authors.initials: J
authors.lastname: Moolman-Smook
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Kanters
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Corfield
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
mesh_terms: D053840:Brugada Syndrome / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D062552:NAV1.3 Voltage-Gated Sodium Channel; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062549:Voltage-Gated Sodium Channel beta-3 Subunit
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; C418492:KCNE3 protein, human; D062552:NAV1.3 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C470379:SCN1B protein, human; C424715:SCN3A protein, human; C493324:SCN3B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062549:Voltage-Gated Sodium Channel beta-3 Subunit