Apolipoprotein E2 (Arg-136-->Cys), a variant of apolipoprotein E associated with late-onset dominance of type III hyperlipoproteinaemia.
Type III hyperlipoproteinaemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (arg-158-->Cys). We identified a 46-year-old white female with severe hyperlipidaemia and the heterozygous apo E3/2* phenotype. Typical clinical characteristics of type III HLP, i.e. palmar xanthomas (orange-yellowish discolorations of the palmar creases) and tuberoeruptive xanthomas, were present in the patient. Without therapy the patient's serum triglycerides (1.098 mg dL(-1)), cholesterol (546 mg dL(-1)), very low-density lipoprotein (VLDL) cholesterol (372 mg dL(-1)) and the apo E concentration (25.0 mg dL(-1)) were distinctly elevated as well as her VLDL cholesterol to serum triglyceride (TG) ratio at 0.34 (normal ratio about 0.2). Direct sequencing of polymerase chain reaction (PCR)-amplified segments of the apo epsilon gene identified a thymine for cytosine (C-->T) exchange in the first base of codon 136 that is predictive for a Cys (TGC) for Arg (CGC) substitution in the encoded amino acid sequence. Two children, an 18-year-old female with the heterozygous apo E4/2* phenotype, a 25-year-old female with the heterozygous apo E3/2* phenotype and the 73-year-old father of the proband with the heterozygous apo E3/2* phenotype are also carriers of the rare mutant. The father has severe atherosclerosis and lipid values compatible with the diagnosis of type III HLP. The affected children have hyper/dyslipidaemia but as yet no clinical expression of the disease. We propose that in the analysed family this rare apo E2 (Arg-136-->Cys) variant is associated with late-onset dominance of type III HLP.
Feussner
G
G
Medizinische Universitätsklinik Heidelberg, Germany.
Albanese
M
M
Mann
W A
WA
Valencia
A
A
Schuster
H
H
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D053329:Apolipoprotein E2; D001057:Apolipoproteins E / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000235:genetics* / Q000378:metabolism*; D007525:Isoelectric Focusing; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA
D053329:Apolipoprotein E2; D001057:Apolipoproteins E; D008074:Lipoproteins; D006493:Heparin; D001120:Arginine; D003545:Cysteine