Marked high density lipoprotein deficiency due to apolipoprotein A-I Tomioka (codon 138 deletion).
We report a novel apolipoprotein A-I (apoA-I) mutation identified in a 64-year-old patient with marked plasma high density lipoprotein (HDL) cholesterol (4 mg/dl) and apoA-I (5mg/dl) deficiency, prior myocardial infarction, and moderate corneal opacities. Coronary angiography revealed extensive atherosclerosis in all three major vessels. Genomic DNA sequencing of the proband revealed a homozygous novel deletion of two successive adenine residues in codon 138 in the apoA-I gene, resulting in a frameshift mutation at amino acid residues 138-178, which we have designated as apoA-I Tomioka. His elder brother was also homozygous for apoA-I Tomioka with marked HDL cholesterol and apoA-I deficiency, but had no clinical evidence of coronary heart disease. Other family members including three siblings and two sons were heterozygous for the mutation, and had approximately 50% of normal plasma HDL cholesterol, and apoA-I. Analysis of apoA-I-containing HDL particles by two-dimensional gel electrophoresis revealed undetectable apoA-I HDL particles in the homozygotes, while in heterozygotes, the mean concentrations of apoA-I in large alpha-1 and very small prebeta-1 HDL subpopulations were significantly decreased at about 35% of normal. Thus, apoA-I Tomioka, a novel deletion mutation in codon 138 of the apoA-I gene, is the causative defect in this case of HDL deficiency.
Wada
Masamichi
M
Tomioka General Hospital, Cardiology Division, Tomioka, Gunma, Japan.
Iso
Tatsuya
T
Asztalos
Bela F
BF
Takama
Noriaki
N
Nakajima
Tadashi
T
Seta
Yukihiro
Y
Kaneko
Katsumi
K
Taniguchi
Yasuhiro
Y
Kobayashi
Hideo
H
Nakajima
Katsuyuki
K
Schaefer
Ernst J
EJ
Kurabayashi
Masahiko
M
D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003062:Codon; D003318:Corneal Opacity / Q000235:genetics; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006322:Heart Aneurysm / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007009:Hypolipoproteinemias / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003062:Codon; D014280:Triglycerides