Browsing by Author "Langenhoven, E."

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    The identification of two low-density lipoprotein receptor gene mutations in South African familial hypercholesterolaemia
    (Health & Medical Publishing Group, 1989) Kotze, M. J.; Langenhoven, E.; Warnich, Louise; Du Plessis, L.; Marx, M. P.; Oosthuizen, C. J. J.; Retief, A. E.
    Two point mutations were discovered in the low-density lipoprotein genes of patients with familial hypercholesterolaemia (FH). Defective genes were cloned and/or amplified by the polymerase chain reaction (PCR) method and the DNA sequences determined. A guanine to adenine base transition in exon 4 was found to be the molecular defect in 20% of cases of FH in the Afrikaner population. A second mutation, a guanine to adenine base substitution in exon 9, was identified in two homozygous FH individuals. Restriction enzyme analysis of PCR-amplified DNA from blood and tissue samples now permits accurate diagnosis of these mutations.
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    Molecular characterisation of a low-frequency mutation in exon 8 of the human low-density lipoprotein receptor gene
    (Health & Medical Publishing Group, 1989) Kotze, M. J.; Langenhoven, E.; Warnich, Louise; Marx, M. P.; Retief, A. E.
    The prevalence of familial hypercholesterolaemia (FH), an autosomal dominant disease characterised by raised low-density lipoprotein (LDL) cholesterol levels, is at least five times higher in the white Afrikaner population than in most other population groups in the world. A founder gene effect has been suggested to explain this abnormally high frequency. Detection of a polymorphic Stu I site in the 5' region of the LDL receptor gene and association of both restriction fragment length polymorphism alleles with FH in Afrikaners, indicated the existence of at least two founder members of the disease in this population. DNA from a hetero-allelic FH homozygote from this South African group has been analysed through genomic cloning and sequencing. The DNA polymorphic site is caused by a single guanine to adenine transition within exon 8 of the LDL receptor gene and can be used in the determination of haplotype-associated defects.
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    Recurrent 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.