Deficiency of cholesteryl ester transfer protein. Description of the molecular defect and the dissociation of cholesteryl ester and triglyceride transport in plasma.

A patient is described who exhibited, despite excessively high postprandial triglyceride levels, high levels of HDL cholesterol. Measurement of CETP activity and mass in the patient's plasma showed values of less than 5% and 2%, respectively, of a normolipidemic plasma pool. The CETP cDNA of the patient exhibited a mutation (T-->G), turning codon 57 (TAT) of exon 2 into a stop codon (TAG) and abolishing a, XcmI restriction site. Digestion of directly amplified CETP cDNA from the patient with XcmI indicated the exclusive presence of CETP cDNA containing the mutation. Analysis of the corresponding region of the CETP gene indicated the patient to be heterozygous for the nonsense mutation at codon 57, a finding that can only be explained by the presence of a null allele in addition to the allele with the nonsense mutation. The combination of TG intolerance of uncertain cause, together with CETP deficiency due to a novel mutation, produced the paradoxical constellation--high levels of HDL cholesterol (172 mg/dL) associated with a high post-prandial lipemia of 1460 mg triglycerides/dL.8 hours--and provided further insight into the role of CETP as mediator between pools of triglycerides and cholesteryl esters in plasma.