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Two Japanese siblings with markedly increased HDL are found homozygous for a CETP intron-14 splice-site mutation eliminating the protein (Nature 1989)
Original title: Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins
Increased HDL sometimes clusters in families, but a clear genetic basis had not previously been documented. Because CETP catalyzes cholesteryl ester transfer from HDL to other lipoproteins, it might influence HDL levels. Using monoclonal antibodies, the authors showed CETP was absent in two Japanese siblings with markedly increased and enlarged HDL. The siblings were homozygous for a point mutation in the 5-prime splice donor site of intron 14 of the CETP gene, a change incompatible with normal pre-messenger RNA splicing. The results indicate this family has an inherited CETP deficiency due to a gene splicing defect, illustrating the key role CETP plays in human HDL metabolism.
Original abstract
Plasma high density lipoproteins (HDL) are a negative risk factor for atherosclerosis. Increased HDL is sometimes clustered in families, but a genetic basis has never been clearly documented. The plasma cholesteryl ester transfer protein (CETP) catalyses the transfer of cholesteryl ester from HDL to other lipoproteins and therefore might influence HDL levels. Using monoclonal antibodies, we show that CETP is absent in two Japanese siblings who have markedly increased and enlarged HDL. Furthermore, they are homozygous for a point mutation in the 5'-splice donor site of intron 14 of the gene for CETP, a change that is incompatible with normal splicing of pre-messenger RNA. The results indicate that the family has an inherited deficiency of CETP due to a gene splicing defect, and illustrate the key role that CETP has in human HDL metabolism.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.