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

• Published in: Atherosclerosis Vol. 124; no. 2; pp. 183 - 189
• Main Authors: Hoffer, Mariëtte J.V, Niththyananthan, Sarojinidevi, Naoumova, Rossitza P, Kibirige, Mohammed S, Frants, Rune R, Havekes, Louis M, Thompson, Gilbert R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 02-08-1996; Elsevier
• Subjects: Adult; Anticholesteremic Agents - therapeutic use; Apolipoprotein E; Apolipoproteins E - blood; Apolipoproteins E - drug effects; Apolipoproteins E - genetics; Biological and medical sciences; Child; Child, Preschool; Cholesterol - blood; Cholestyramine Resin - therapeutic use; Cysteamine - therapeutic use; Dinucleotide Repeats - genetics; Disorders of blood lipids. Hyperlipoproteinemia; DNA - analysis; Dyslipidaemia; Electrophoresis; Exons; Female; Fenofibrate; Fenofibrate - therapeutic use; Genotype; Humans; Hyperlipoproteinemia Type III - blood; Hyperlipoproteinemia Type III - drug therapy; Hyperlipoproteinemia Type III - genetics; Hypolipidemic Agents - therapeutic use; Immunoblotting; Male; Medical sciences; Metabolic diseases; Nuclear Family; Phenotype; Point mutation; Point Mutation - genetics; Radiation-Protective Agents - therapeutic use; Triglycerides - blood; Fenofibrate; Dyslipidaemia; Apolipoprotein E; Point mutation; Human; Metabolic diseases; Exploration; Lipids; Hyperlipoproteinemia
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(96)05819-4

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).