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Apolipoprotein E1-Hammersmith (Lys146 → Asn;Arg147 → Trp), due to a dinucleotide substitution, is associated with early manifestation of dominant type III hyperlipoproteinaemia

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Author: Hoffer, M.J.V. · Niththyananthan, S. · Naoumova, R.P. · Kibirige, M.S. · Frants, R.R. · Havekes, L.M. · Thompson, G.R.
Institution: Gaubius Instituut TNO
Source:Atherosclerosis, 2, 124, 183-189
Identifier: 233418
doi: doi:10.1016/0021-9150(96)05819-4
Keywords: 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


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