A New Case of ApoA-I Deficiency Showing Codon 8 Nonsense Mutation of the ApoA-I Gene Without Evidence of Coronary Heart Disease

Abstract

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.

Insulin Resistance and Angiographical Characteristics of Coronary Atherosclerosis

“…When stenotic coronary arteries were found, the presence of stenosis was determined using a computer-assisted CAG analysis system (Mipron 1; Kontron Co) after the direct intracoronary injection of isosorbide dinitrate (ISDN; 2.5 mg/5 ml solution over 20 s). [15][16][17] One minute after the injection of ISDN through the Judkins catheter, CAG was performed from several projections. The severity of coronary atherosclerosis was defined by the number of diseased coronary arteries (>50% luminal narrowing), and angiographical characteristics of coronary atherosclerotic lesions (ie, the severity of CHD) were defined by the GS, based on the hypothesis that the severity of CHD should be considered as a consequence of the functional significance of the vascular narrowing and the extent of the area perfused by the involved vessel or vessels.…”

Associations Among Serum Lipoprotein(a) Levels, Apolipoprotein(a) Phenotypes, and Myocardial Infarction in Patients With Extremely Low and High Levels of Serum Lipoprotein(a)

“…One minute after the injection of ISDN through the Judkins catheter, which took 20 s, CAG was performed from several projections during 7 min, as described previously. 25,26 Determination of Serum Lipids, Lipoproteins, Apolipoproteins, and Apo(a) Isoform Phenotype A blood sample was drawn in the morning after an overnight fast. Serum total cholesterol (TC) and triglyceride (TG) concentrations were determined enzymatically.…”

Cellular Cholesterol Transport and Efflux in Fibroblasts Are Abnormal in Subjects With Familial HDL Deficiency

“…With the exception of the drug probucol, medication does not account for severe HDL deficiency. Known causes of severe HDL deficiency have been reviewed recently and include apoA-I gene rearrangements and nonsense mutations, 10 some of the apoA-I point mutations (nϭ22), 11 lecithin:cholesterol acyltransferase (LCAT) deficiency, 12 and Tangier disease. 13,14 Severe hypertriglyceridemia, caused by lipoprotein lipase (LPL) gene defects, apoC-II deficiency (an activator of LPL), or other (yet-unknown) factors, is associated with severe reductions of HDL-C levels.…”