Mutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics

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dc.contributor.authorPeeters A.V.
dc.contributor.authorVan Gaal L.F.
dc.contributor.authorDu Plessis L.
dc.contributor.authorLombardi M.P.R.
dc.contributor.authorHavekes L.M.
dc.contributor.authorKotze M.J.
dc.date.accessioned2011-05-15T15:59:11Z
dc.date.available2011-05-15T15:59:11Z
dc.date.issued1997
dc.description.abstractDNA samples from 100 unrelated Belgian patients with familial hypercholesterolemia (FH) were screened for the presence of specific low-density lipoprotein receptor (LDLR) gene mutations, previously shown to be prevalent in related populations. Two point mutations, viz., P664L and a G to A splicing defect at position 1359-1, were detected in single Flemish-speaking families. A long-distance polymerase chain reaction (PCR) assay, used to screen for the 4-kb and 2.5-kb deletions previously identified by Southern blot analyses in different parts of The Netherlands, revealed a 3-kb deletion in two Belgian patients. Comparison of PCR product length showed that both Dutch deletions of exons 7-8 are identical to that found in Belgians, but different from the 2.5-kb deletion previously described in South Africans of mixed ancestry. The Belgian patients probably share a common ancestor, for each mutation identified, with FH patients from The Netherlands, since all three mutations were associated with the same LDLR gene haplotype as described for the Dutch population. Analysis of the deletion junctions demonstrated the role of a 31-bp repetitive sequence in the generation of large rearrangements involving exons 7 and 8 of the LDLR gene. The finding that only 4 out of 100 analyzed Belgian hypercholesterolemics carry a known LDLR mutation that is prevalent in related populations suggests that the Belgian FH population has its own spectrum of mutations.
dc.description.versionArticle
dc.identifier.citationHuman Genetics
dc.identifier.citation100
dc.identifier.citation2
dc.identifier.issn3406717
dc.identifier.other10.1007/s004390050503
dc.identifier.urihttp://hdl.handle.net/10019.1/11048
dc.subjectlow density lipoprotein receptor
dc.subjectarticle
dc.subjectbelgium
dc.subjectcomparative study
dc.subjectcontrolled study
dc.subjectexon
dc.subjectfamilial hypercholesterolemia
dc.subjectgene deletion
dc.subjectgene mutation
dc.subjectgene rearrangement
dc.subjectgene sequence
dc.subjecthaplotype
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmajor clinical study
dc.subjectnetherlands
dc.subjectpoint mutation
dc.subjectpolymerase chain reaction
dc.subjectpriority journal
dc.subjectreceptor gene
dc.subjectsouthern blotting
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBase Sequence
dc.subjectBelgium
dc.subjectCloning, Molecular
dc.subjectFemale
dc.subjectGenetic Screening
dc.subjectHaplotypes
dc.subjectHumans
dc.subjectHyperlipoproteinemia Type II
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMolecular Sequence Data
dc.subjectMutation
dc.subjectNetherlands
dc.subjectPolymerase Chain Reaction
dc.subjectReceptors, LDL
dc.subjectSequence Analysis, DNA
dc.subjectSequence Deletion
dc.titleMutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics
dc.typeArticle
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