Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.
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A kindred with apolipoprotein E deficiency and a truncated lower molecular weight apoE mutant, designated apoE-3Washington, has been identified. Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Plasma apoE levels in the proband were approximately 4% of normal. This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia. Sequence analysis of the patient's apoE gene revealed a single nucleotide substitution of an A for a G, which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with a molecular mass of 23.88 kDa. Northern blot analysis of differentiated monocyte-derived macrophages demonstrated a mutant mRNA indistinguishable in size from normal apoE mRNA. The nucleotide substitution also resulted in the formation of a new restriction site for Mae I. Using this enzyme we were able to establish that the proband is a homozygote and that her two offsprings are heterozygous for the epsilon-3Washington allele. These data demonstrate that the striking deficiency of apoE-3Washington results in a moderate form of type III hyperlipoproteinemia. The clinica…
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Cases of apoE deficiency have been reported, but none included neurocognitive or retinal function studies.
“Cases of apoE deficiency have been reported,4-9 but none included neurocognitive or retinal function studies.”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [8]
Two case-studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects.
“Furthermore, two case‐studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects, and one case‐control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08) 39 , 40 , 41”
From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [41]
One case-control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08).
“Furthermore, two case‐studies of patients with frameshift mutations and premature stop codons in exon 4 did not observe clear neurocognitive defects, and one case‐control study found a higher frequency of a combined Glu262Lys and Glu263Lys variant in patients with memory complaints (P = .08) 39 , 40 , 41”
From <i>APOE</i> and dementia – resequencing and genotyping in 105,597 individuals (2020) · cites this paper as [41]
Studies of familial apoE deficiency describe persons examined in their 40s without neurological defects, although peripheral lipid metabolism was affected.
“Finally, studies of familial apoE deficiency describe persons examined in their 40s without neurological defects, although the peripheral lipid metabolism was affected [27,97].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [97]
Of the 11 cases of APOE deficiency with reported mutation sites, four were homozygotes and seven were compound heterozygotes or heterozygotes.
“Of the 11 cases of APOE deficiency with reported mutation sites, four were homozygotes and seven were compound heterozygotes or heterozygotes27, 29-40).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [36]
Homozygotes for APOE3 Washington (Trp210Ter) showed relatively mild type III HLP, possibly due to the structure of apoE retaining the N-terminal side.
“Meanwhile, homozygotes for APOE3 Washington (Trp210Ter) showed relatively mild type III HLP, possibly due to the structure of apoE retaining the N-terminal side (Table 1)36).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [36]
The proband in that other case was homozygous for this mutation, leading to a moderate form of type III HLP.
“The proband was homozygous for this mutation, leading to a moderate form of type III HLP.”
From Severe xanthomatosis associated with familial apolipoprotein E deficiency. (1996) · cites this paper as [12]
In the other patient with familial apo E deficiency, a single nucleotide substitution of A for G converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), leading to synthesis of a truncated apo E peptide of 209 instead of the normal 299 amino acids.
“In the other case a single nucleotide substitution of an A for a G was identified, which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated apo E peptide of 209 instead of the normal 299 amino acids.'2”
From Severe xanthomatosis associated with familial apolipoprotein E deficiency. (1996) · cites this paper as [12]
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- Authors
- Lohse, P., Brewer, H., Meng, M., Skarlatos, S., LaRosa, J., & Brewer, H.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 1992-11
- Volume
- 33
- Issue
- 11
- Pages
- 1583-1590
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2340994834
- Cited by
- 59
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E deficiency, type III hyperlipoproteinemia, premature stop codon, hypertriglyceridemia, serum cholesterol, homozygosity, restriction site mutations, monocyte-derived macrophages, nervous system function, immune regulation
- MeSH terms
- Apolipoproteins E, Base Sequence, Codon, DNA, DNA Mutational Analysis, Female, Humans, Hyperlipoproteinemia Type II, Middle Aged, Molecular Sequence Data, Polymorphism, Restriction Fragment Length, Electrophoresis, Gel, Two-Dimensional
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