Mutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics
Date
1997
Authors
Peeters A.V.
Van Gaal L.F.
Du Plessis L.
Lombardi M.P.R.
Havekes L.M.
Kotze M.J.
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Journal ISSN
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Abstract
DNA 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.
Description
Keywords
low density lipoprotein receptor, article, belgium, comparative study, controlled study, exon, familial hypercholesterolemia, gene deletion, gene mutation, gene rearrangement, gene sequence, haplotype, human, human cell, major clinical study, netherlands, point mutation, polymerase chain reaction, priority journal, receptor gene, southern blotting, Adolescent, Adult, Aged, Aged, 80 and over, Base Sequence, Belgium, Cloning, Molecular, Female, Genetic Screening, Haplotypes, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Molecular Sequence Data, Mutation, Netherlands, Polymerase Chain Reaction, Receptors, LDL, Sequence Analysis, DNA, Sequence Deletion
Citation
Human Genetics
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100
2