Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population
Date
2001
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Health & Medical Publishing Group
Abstract
Objective. Familial hypercholesterolaemia (FH) is a common genetic disease characterised by strikingly elevated plasma cholesterol concentration, which can lead to premature coronary death if left untreated. In this study DNA diagnosis of FH, which allows detection before onset of clinical symptoms, was evaluated against biochemical parameters routinely used to identify subjects with FH. Design. A population-based strategy was used to identify low-density lipoprotein receptor (LDLR) gene defects in South Africans with clinical signs of FH, followed by a family-based DNA screening approach for presymptomatic diagnosis of FH. Results. DNA screening of 790 at-risk relatives for the FH-related mutations identified in 379 index cases, allowed accurate disease diagnosis in an additional 338 relatives and exclusion of the relevant mutation in 452 individuals. The sensitivity and specificity of the diagnosis, based on total cholesterol values measured in family members of FH heterozygous index cases with one of the three founder-related mutations, D154N, D206E and V408M, were 89.3% and 81.9%, respectively. Conclusion. The predominance of 10 LDLR gene mutations in the local populations justifies population-directed DNA diagnosis of FH in South Africa on a routine basis, particularly since expression of the defective gene measured in biochemical tests does not allow accurate diagnosis of FH in all cases. DNA testing provides a definitive tool for family tracing aimed at pre-clinical diagnosis and preventive treatment of FH.
Description
CITATION: Vergotine, J., Thiart, R. & Kotze, M. J. 2001. Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population. South African Medical Journal, 91(12):1053-1059.
The original publication is available at http://www.samj.org.za
The original publication is available at http://www.samj.org.za
Keywords
Hypercholesteremia
Citation
Vergotine, J., Thiart, R. & Kotze, M. J. 2001. Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population. South African Medical Journal, 91(12):1053-1059.