Cholesteryl ester transfer protein deficiency caused by a nonsense mutation detected in the patient's macrophage mRNA.

Cholesteryl ester transfer protein (CETP) deficiency causes marked elevation of plasma high-density lipoproteins, termed hyperalphalipoproteinemia. Only one CETP mutation has been found previously, partly because the relative unavailability of CETP mRNA has hampered analysis. We demonstrated CETP mRNA expression in the monocyte-derived macrophages and identified a new CETP mutation by analyzing the macrophage mRNA of a homozygous patient with familial form of hyperalphalipoproteinemia. The nonsense mutation at codon 309 in exon 10 of the CETP gene was thought to delete the carboxy-terminal third and caused a decrease in the level of CETP mRNA. Our findings provide more evidence that CETP mutations may underlie a subset of familial hyperalphalipoproteinemia.