A newly identified heterozygous lipoprotein lipase gene mutation (Cys239-->stop/TGC972-->TGA; LPLobama) in a patient with primary type IV hyperlipoproteinemia.

We investigated measures for identification of heterozygous lipoprotein lipase (LPL) deficiency in unrelated subjects with primary type IV hyperlipoproteinemia in order to acquire a helpful clue for understanding the correlation between hypertriglyceridemia and the status of being a heterozygous carrier of an LPL gene variant. Identification of heterozygous LPL deficiency was performed by monitoring the immunoreactive LPL mass in postheparin plasma (PHP) using our developed sandwich-enzyme immunoassay technique for first screening. Then, in subjects found to have half or less than half of the control LPL mass value in PHP, the polymerase chain reaction-single strand conformation polymorphism method was used to detect LPL gene aberrations as a second screening. This approach was evaluated as being useful as it succeeded in identifying a subject (proband KD) with heterozygous LPL deficiency. The mutation in the LPL gene of proband KD was newly characterized as a nucleotide C972 to A transversion in exon 6, resulting in substitution of a premature termination codon (TGA) for Cys239 (TGC). This nonsense mutation, designated as LPLobama, creates an MboI restriction site and eliminates an HgiAI restriction site, and this allows rapid screening of subjects with type IV as well as type I hyperlipoproteinemia for the mutation. The homozygous state for the LPLobama allele resulted in neither detectable LPL activity nor immunoreactive LPL mass in PHP, and this was seen in two of proband KD's siblings.