Browsing by Author "Oosthuizen, C. J. J."
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- ItemRecurrent LDL-receptor mutation causes familial hypercholesterolaemia in South African coloureds and Afrikaners(Health & Medical Publishing Group, 1995) Kotze, M. J.; Langenhoven, E.; Theart, L.; Loubser, O.; Micklem, A.; Oosthuizen, C. J. J.Three low-density lipoprotein receptor (LDLR) gene mutations were previously shown to cause familial hypercholesterolaemia (FH) in up to 90% of affected Afrikaners. Association of each mutation with a single chromosomal background provided molecular genetic evidence that the proposed 'founder gene effect' was responsible for the high prevalence of FH among white Afrikaners. In this study we report the identification of the FH Afrikaner-2 (FH2) mutation, Val408 to Met, in the so-called coloured population of South Africa, a people of mixed ancestry, with rapid non-radioactive methods for mutation detection. Haplotype analysis with polymorphisms on both sides of the FH2 mutation indicated that the identical LDLR gene mutations found in two different South African population groups were caused by independent events at a potential CpG mutational 'hot spot'. The allelic variation giving rise to the different chromosomal backgrounds of the FH2 mutation does not affect the properties of the abnormal LDLR protein product which causes FH in these subjects. This mutation is thus expected to cause the same severe form of FH in affected coloureds as was previously demonstrated in Afrikaners. Detection of mutant LDLR gene alleles in polymerase chain reaction products, directly after gel electrophoresis, now allows accurate presymptomatic diagnosis of the FH2 mutation in FH patients from two different South African population groups.
- ItemThe use of DNA markers in the pre-clinical diagnosis of familial adenomatous polyposis in families in South Africa(Health & Medical Publishing Group, 1995) Grobbelaar, J. J.; Oosthuizen, C. J. J.; Madden, M. V.; Bailey, S. E.; Retief, A. E.; Kotze, M. J.Haplotype association studies were performed in 10 unrelated South African families and 1 German immigrant family with familial adenomatous polyposis (FAP). Three DNA probes, recognising five restriction fragment length polymorphisms (RFLPs) around the gene locus for FAP on chromosome 5q, were used. The RFLP analysis was informative or partially informative in all the families studied. Five haplotypes were found to segregate with the disease locus. The predominant association of two of these haplotypes with FAP in the South African families suggests that two mutations may cause the disease in about 70% of families in this population. Meiotic recombination events were detected between the FAP gene and probe M4 (D5S6), but not probes Pi227 (D5S37) and C11p11 (D5S71). Haplotype analysis allowed the preclinical diagnosis of FAP in 5 subjects.