An exon 4 mutation identified in the majority of South African familial hypercholesterolaemics

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dc.contributor.authorKotze M.J.
dc.contributor.authorWarnich L.
dc.contributor.authorLangenhoven E.
dc.contributor.authorDu Plessis L.
dc.contributor.authorRetief A.E.
dc.date.accessioned2011-05-15T16:03:36Z
dc.date.available2011-05-15T16:03:36Z
dc.date.issued1990
dc.description.abstractThe prevalence of familial hypercholesterolemia (FH) is significantly higher in the Afrikaans speaking population (Afrikaners) of South Africa than reported in most other populations. A founder gene effect has been proposed to explain the high FH frequency, implying that the same low density lipoprotein (LDL) receptor gene defect is present in the majority of affected Afrikaners. By using DNA amplification and sequence determination, we have detected a point mutation in DNA from two Afrikaner FH homozygotes. A cytosine to guanine base substitution at nucleotide position 681 of the LDL receptor cDNA results in an amino acid change from aspartic acid to glutamic acid at residue 206 in the cysteine rich ligand binding domain of the LDL receptor. Since three previously mapped transport deficient alleles of the LDL receptor were also traced to cysteine rich repeats of the protein, these results suggest that the mutation is responsible for the receptor defective mutation predominantly found in Afrikaner FH homozygotes. The mutation gives rise to an additional DdeI restriction site in DNA of affected subjects and segregation of the mutation with the disease was confirmed in five large Afrikaner FH families. We predict that 65% of affected South African Afrikaners carry this particular base substitution. Amplification of genomic DNA, using the polymerase chain reaction method, and restriction enzyme analysis now permit accurate diagnosis of the mutation in subjects with FH.
dc.description.versionArticle
dc.identifier.citationJournal of Medical Genetics
dc.identifier.citation27
dc.identifier.citation5
dc.identifier.issn222593
dc.identifier.urihttp://hdl.handle.net/10019.1/12692
dc.subjectarticle
dc.subjectcase report
dc.subjectethnic or racial aspects
dc.subjectexon
dc.subjectfamilial hypercholesterolemia
dc.subjectgenetic engineering
dc.subjectheredity
dc.subjecthomozygote
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmutant
dc.subjectnucleic acid base substitution
dc.subjectpriority journal
dc.subjectrestriction fragment length polymorphism
dc.subjectsouth africa
dc.subjectAlleles
dc.subjectCase Report
dc.subjectDNA
dc.subjectExons
dc.subjectFemale
dc.subjectGene Frequency
dc.subjectHuman
dc.subjectHypercholesterolemia, Familial
dc.subjectMale
dc.subjectMutation
dc.subjectPedigree
dc.subjectPolymerase Chain Reaction
dc.subjectReceptors, LDL
dc.subjectSouth Africa
dc.subjectSupport, Non-U.S. Gov't
dc.titleAn exon 4 mutation identified in the majority of South African familial hypercholesterolaemics
dc.typeArticle
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