Long QT syndrome in South Africa: the results of comprehensive genetic screening.
Congenital long QT syndrome (cLQTS) is a genetic disorder predisposing to ventricular arrhythmia, syncope and sudden death. Over 700 different cLQTS-causing mutations in 13 genes are known. The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening). Fourteen disease-causing mutations were identified, eight (including the founder mutation) in KCNQ1, five in KCNH2 and one in KCNE1. Two mutations were novel. Two double heterozygotes were found among the 23 families (8.5%) carrying the founder mutation. In conclusion, cLQTS in South Africa reflects both a strong founder effect and a genetic spectrum similar to that seen in other populations. Consequently, five-gene screening should be offered as a standard screening option, as is the case internationally. This will disclose compound and double heterozygotes. Fivegene screening will most likely be even more informative in other South African sub-populations with a greater genetic diversity.
US/MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Stellenbosch, South Africa.
Paula L
PL
Hedley
Glenda A
GA
Durrheim
Firzana
F
Hendricks
Althea
A
Goosen
Cathrine
C
Jespersgaard
Birgitte
B
Støvring
Tam T
TT
Pham
Michael
M
Christiansen
Paul A
PA
Brink
Valerie A
VA
Corfield
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult