Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

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dc.contributor.authorThiart, R.
dc.contributor.authorScholtz, C. L.
dc.contributor.authorVergotine, J.
dc.contributor.authorHoogendijk, C. F.
dc.contributor.authorDe Villiers, J. N. P.
dc.contributor.authorNissen, H.
dc.contributor.authorBrusgaard, K.
dc.contributor.authorGaffney, D.
dc.contributor.authorHoffs, M. S.
dc.contributor.authorVermaak, W. J.
dc.contributor.authorKotze, M. J.
dc.date.accessioned2013-01-23T10:11:25Z
dc.date.available2013-01-23T10:11:25Z
dc.date.issued2000-02
dc.descriptionThe original publication is available at http://jmg.bmj.com/en_ZA
dc.description.abstractIn South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenicLDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.en_ZA
dc.description.sponsorshipHarry and Doris Crossley Foundationen_ZA
dc.description.sponsorshipSouth African Medical Research Councilen_ZA
dc.description.sponsorshipUniversity of Stellenbosch
dc.description.sponsorshipBritish Heart Foundation (grant no PG/96013)
dc.description.versionPublisher's version
dc.format.extent12 p.
dc.identifier.citationThiarta, R et al. 2000. Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia. J Med Genet 2000;37(7):514-519 doi:10.1136/jmg.37.7.514.en_ZA
dc.identifier.issn1468-6244 (online)
dc.identifier.otherdoi:10.1136/jmg.37.7.514
dc.identifier.urihttp://hdl.handle.net/10019.1/73387
dc.language.isoen_ZAen_ZA
dc.publisherBMJ Publishing Group Ltd.en_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectLow density lipoproteinsen_ZA
dc.subjectHypercholesterolaemia -- Cross-cultural studiesen_ZA
dc.subjectGenetic disorders -- Diagnosisen_ZA
dc.subject.lcshHypercholesterolaemia -- Genetic aspects
dc.titlePredominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemiaen_ZA
dc.typeArticleen_ZA
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