Genetics
First Caucasian North American case of CETP deficiency traced to a novel exon 9 stop mutation (J Lipid Res 1998)
Original title: Human plasma CETP deficiency: identification of a novel mutation in exon 9 of the CETP gene in a Caucasian subject from North America
A 57-year-old female Nova Scotian subject with no Japanese ancestry, homozygous for a novel CETP gene mutation, was characterized for plasma lipoprotein phenotype and molecular defect, since most previously identified CETP-deficiency mutations occur in Japanese populations. Her total cholesterol was 7.3 mmol/l with LDL cholesterol 2.9 mmol/l, HDL cholesterol markedly elevated at 4.4 mmol/l, apoA-I 256 mg/dl, and apoE 14.4 mg/dl, with only slightly reduced apoB at 94 mg/dl; her VLDL and LDL were cholesteryl ester-poor and triacylglycerol-rich while her HDL was cholesteryl ester-rich, and no plasma CETP activity or mass was detected. Bidirectional DNA sequencing of all 16 exons identified a single base substitution in exon 9 (C to T at nucleotide 836, causing 268 Arg to STOP) in both alleles, with no other mutation found, and a rapid PCR-RFLP screening test was designed for this variant. The authors report this as the first Caucasian North American patient identified with CETP deficiency.
Original abstract
Human plasma cholesteryl ester transfer protein (CETP) is a 476-residue hydrophobic glycoprotein that catalyzes the heterotransfer of cholesteryl esters and triacylglycerols among lipoproteins: Mutations in the CETP gene have been identified, mostly in the Japanese population. These mutations result in hypercholesterolemia due to the presence of large cholesteryl ester-rich HDL particles, elevated plasma apoA-I and apoE, and reduced apoB levels. Here we report the plasma lipoprotein phenotype and molecular defect in a 57-year-old female Nova Scotian subject lacking Japanese ancestry who is homozygous for a novel mutation in the CETP gene. Her total plasma cholesterol was 7.3 mmol/l with an LDL cholesterol of 2.9 mmol/l and HDL cholesterol of 4.4 mmol/l. She was mildly hypertriglyceridemic (1.6 mmol/l) and had markedly elevated apoA-I (256 mg/dl) and apoE (14.4 mg/dl) with only slightly reduced apo/B levels (94 mg/dl). Her VLDL and LDL were cholesteryl ester-poor (1.8 and 37.2% of lipids, respectively) and triacylglycerol-rich (67.3 and 18.9% of lipids, respectively) while her HDL was cholesteryl ester-rich (40.2-45.7% of lipids) and triacylglycerol-poor (3.3-2.5% of lipids). No plasma CETP activity or mass was detected. Bi-directional DNA sequence analysis of PCR products from all 16 exons showed a single base substitution (C-->T at nucleotide 836 in exon 9 resulting in 268 Arg-->STOP) in both alleles. No other mutation was detected. A single base mismatched, 26 bp reverse PCR primer that produced a single Mae III RFLP site upon amplification of the mutated DNA sequence was designed for rapid population screening. This subject is, we believe, the first Caucasian North American patient reported to have CETP deficiency.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.