Apolipoprotein E-4Philadelphia (Glu13—-Lys,Arg145—-Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia
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The molecular defect in a 24-year-old white female with severe type III hyperlipoproteinemia has been elucidated. The patient's apolipoprotein (apo) E migrated in the apoE-4 position on isoelectric focusing gels. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis the apoE-4 variant had a smaller apparent molecular weight than apoE-4(Cys112----Arg). Sequence analysis of DNA amplified with the polymerase chain reaction revealed two nucleotide substitutions in the proband's apoE gene. A C to T mutation converted arginine (CGT) at position 145 of the mature protein to cysteine (TGT) thus creating the apoE-2 variant. A second G to A substitution at amino acid 13 led to the exchange of lysine (AAG) for glutamic acid (GAG), thereby adding 2 positive charge units to the protein and producing the apoE-5 variant. Computer analysis of the apoE-4Philadelphia gene revealed that the G to A mutation in exon 3 resulted in the loss of an AvaI restriction enzyme site. The second mutation, a C to T substitution in the fourth exon of the apoE gene, eliminated a cleavage site for the enzyme BbvI. Using these restriction fragment length polymorphisms as well as DNA sequence analysis we have demonstrated that the patient is homozygous for both point mutations in the apoE gene.
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Severe type III HLP has been reported in APOE4 Philadelphia (Glu13Lys, Arg145Cys) homozygotes.
“Furthermore, severe type III HLP has been reported in APOE4 Philadelphia (Glu13Lys, Arg145Cys) homozygotes63)”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [63]
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Self-citationImpact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
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- Authors
- Lohse, P., Mann, W. A., Stein, E. A., & Brewer, H. B.
- Affiliations
- National Institutes of Health (US)
- Christ Hospital (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-06
- Volume
- 266
- Issue
- 16
- Pages
- 10479-10484
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1733825577
- Cited by
- 54
- References
- 7
- Citations by year
- 2025: 4 · 2022: 2 · 2020: 1 · 2016: 4 · 2015: 2 · 2013: 1
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- apolipoprotein E, type III hyperlipoproteinemia, restriction fragment length polymorphism, molecular defects
- MeSH terms
- Adult, Amino Acid Sequence, Animals, Apolipoproteins E, Arginine, Base Sequence, Cystine, DNA, Electrophoresis, Polyacrylamide Gel, Exons, Female, Glutamine, Humans, Hyperlipoproteinemia Type III, Lysine, Molecular Sequence Data, Mutation, Polymorphism, Restriction Fragment Length, Restriction Mapping, Apolipoprotein E4
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