Title
Apolipoprotein E1-Hammersmith (Lys146 → Asn;Arg147 → Trp), due to a dinucleotide substitution, is associated with early manifestation of dominant type III hyperlipoproteinaemia
Author
Hoffer, M.J.V.
Niththyananthan, S.
Naoumova, R.P.
Kibirige, M.S.
Frants, R.R.
Havekes, L.M.
Thompson, G.R.
Gaubius Instituut TNO
Publication year
1996
Abstract
Apolipoprotein E (apoE) is one of the major protein constituents of chylomicron and very low density lipoprotein (VLDL) remnants and plays a central role as a ligand in the receptor-mediated uptake of these particles by the liver. Here we describe a new variant of apoE, apoE1-Hammersmith, which is associated with dominantly expressed type III hyperlipidaemia. The propositus, aged 26, developed tubero-eruptive xanthomas at the age of 3, her daughter developed similar lesions at age 7 but her son, aged 3, shows no clinical abnormality so far. All three cases had an apoE3E1 phenotype and a broad β band on lipoprotein electrophoresis. Cysteamine modification resulted in a shift of apoE1 to the apoE2 isoform position, indicating that the mutation leading to apoE1-Hammersmith occurred on an apoE3 background. ApoE genotyping confirmed these results. Sequence analysis of DNA of the propositus was performed for exons 3 and 4 and revealed a dinucleotide substitution causing two amino acid changes at adjacent positions (Lys146 → Asn) and (Arg147 → Trp). Chemicals/CAS: Anticholesteremic Agents; Antilipemic Agents; Apolipoproteins E; Cholesterol, 57-88-5; Cholestyramine, 11041-12-6; Cysteamine, 60-23-1; DNA, 9007-49-2; Procetofen, 49562-28-9; Radiation-Protective Agents; Triglycerides
Subject
Biology
Dyslipidaemia
Cclofibrate
Colestyramine
Mercaptamine
Atherosclerosis
Case report
Adult
Anticholesteremic Agents
Antilipemic Agents
Apolipoproteins E
Child
Child, Preschool
Cholesterol
Cholestyramine
Cysteamine
Dinucleotide Repeats
DNA
Electrophoresis
Exons
Female
Genotype
Humans
Hyperlipoproteinemia Type III
Immunoblotting
Male
Nuclear Family
Phenotype
Point Mutation
Procetofen
Radiation-Protective Agents
Triglycerides
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DOI
https://doi.org/10.1016/0021-9150(96)05819-4
TNO identifier
233418
ISSN
0021-9150
Source
Atherosclerosis, 124 (2), 183-189
Document type
article