Apolipoprotein E1-Hammersmith (Lys146 → Asn;Arg147 → Trp), due to a dinucleotide substitution, is associated with early manifestation of dominant type III hyperlipoproteinaemia
article
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
Topics
DyslipidaemiaCclofibrateColestyramineMercaptamineAtherosclerosisCase reportAdultAnticholesteremic AgentsAntilipemic AgentsApolipoproteins EChildChild, PreschoolCholesterolCholestyramineCysteamineDinucleotide RepeatsDNAElectrophoresisExonsFemaleGenotypeHumansHyperlipoproteinemia Type IIIImmunoblottingMaleNuclear FamilyPhenotypePoint MutationProcetofenRadiation-Protective AgentsTriglycerides
TNO Identifier
233418
ISSN
00219150
Source
Atherosclerosis, 124(2), pp. 183-189.
Pages
183-189
Files
To receive the publication files, please send an e-mail request to TNO Repository.