Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible genetic heterogeneity.
Idiopathic ventricular fibrillation in patients with an electrocardiogram (ECG) pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (now frequently called Brugada syndrome) is associated with a high incidence of syncopal episodes or sudden death. The disease is inherited as an autosomal dominant trait. Mutations in SCN5A, a cardiac sodium channel gene, have been recently associated with Brugada syndrome. We have analyzed 7 patients from Israel affected with Brugada syndrome. The families of these patients are characterized by a small number of symptomatic members. Sequencing analysis of SCN5A revealed two novel mutations, G35S and R104Q, in two Brugada patients, and a possible R34C polymorphism in two unrelated controls. No mutations were detected in 5 other patients, suggesting genetic heterogeneity. Low penetrance is probably the cause for the small number of symptomatic members in the two families positive for the SCN5A mutations.
Levy-Nissenbaum
E
E
Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel.
Eldar
M
M
Wang
Q
Q
Lahat
H
H
Belhassen
B
B
Ries
L
L
Friedman
E
E
Pras
E
E
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D002037:Bundle-Branch Block / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000235:genetics*
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels