Apolipoprotein E1-Hammersmith (Lys146-->Asn;Arg147-->Trp), due to a dinucleotide substitution, is associated with early manifestation of dominant type III hyperlipoproteinaemia.
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 beta 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).
Hoffer
M J
MJ
MGC-Department of Human Genetics, Leiden University, The Netherlands.
Niththyananthan
S
S
Naoumova
R P
RP
Kibirige
M S
MS
Frants
R R
RR
Havekes
L M
LM
Thompson
G R
GR
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D002792:Cholestyramine Resin / Q000627:therapeutic use; D003543:Cysteamine / Q000627:therapeutic use; D004247:DNA / Q000032:analysis; D018900:Dinucleotide Repeats / Q000235:genetics*; D004586:Electrophoresis; D005091:Exons; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D015151:Immunoblotting; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D000960:Hypolipidemic Agents; D011837:Radiation-Protective Agents; D014280:Triglycerides; D002792:Cholestyramine Resin; D003543:Cysteamine; D004247:DNA; D002784:Cholesterol; D011345:Fenofibrate