Detection of a new apolipoprotein-E mutation in type III hyperlipidemia using deoxyribonucleic acid restriction isotyping

While determining the apolipoprotein-E (apo-E) genotype of 22 patients with type III hyperlipidemia (HLP III) by restriction isotyping, we identified a new mutant form of apo-E by its unusual DNA restriction fragment length polymorphism pattern. DNA sequence analysis of a polymerase chain reaction-a...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism Vol. 78; no. 3; p. 699
Main Authors: Walden, C C, Huff, M W, Leiter, L A, Connelly, P W, Hegele, R A
Format: Journal Article
Language:English
Published: United States 01.03.1994
Subjects:
Adult
Aged
Alleles
Apolipoproteins E - genetics
Apolipoproteins E - metabolism
Base Sequence
DNA - genetics
Female
Genotype
Humans
Hyperlipoproteinemia Type III - genetics
Male
Molecular Sequence Data
Mutation
Pedigree
Phenotype
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
ISSN:0021-972X
Online Access:Get more information
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Summary:While determining the apolipoprotein-E (apo-E) genotype of 22 patients with type III hyperlipidemia (HLP III) by restriction isotyping, we identified a new mutant form of apo-E by its unusual DNA restriction fragment length polymorphism pattern. DNA sequence analysis of a polymerase chain reaction-amplified portion of the proband's apo-E gene revealed the substitution of cysteine (TGC) for arginine (CGC) at position 136 in the mutant allele (designated R136C). Lipoproteins containing this mutant protein bound defectively to macrophages in vitro, confirming the contribution of R136C to the expression of HLP III in the proband. The proband's two siblings carried the mutant allele and were also heterozygous for E2. Each also had dysbetalipoproteinemia (indicated by the presence of beta-very low density lipoprotein), but neither was hyperlipidemic, attesting to the importance of other factors for the full expression of HLP III. The mutant allele appears to contribute to the inheritance of HLP III in a recessive fashion. Restriction isotyping facilitates the diagnosis of subjects with HLP III, aids in the identification of affected individuals through family screening, and can contribute to the discovery of new mutations that help explain the pathogenesis of HLP III.
ISSN:0021-972X
DOI:10.1210/jc.78.3.699