A NEWLY IDENTIFIED HETEROZYGOUS LIPOPROTEIN-LIPASE GENE MUTATION (CYS(239)-]STOP TGC(972)-]TGA LPL(OBAMA)) IN A PATIENT WITH PRIMARY TYPE-IV HYPERLIPOPROTEINEMIA/

We investigated measures for identification of heterozygous lipoprotei n lipase (LPL) deficiency in unrelated subjects with primary type IV h yperlipoproteinemia in order to acquire a helpful clue for understandi ng the correlation between hypertriglyceridemia and the status of bein g a heterozygous carrier of an LPL gene variant. Identification of het erozygous LPL deficiency was performed by monitoring the immunoreactiv e LPL mass in postheparin plasma (PHP) using our developed sandwich-en zyme immunoassay technique for first screening. Then, in subjects foun d 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 identi fying a subject (proband KD) with heterozygous LPL deficiency. The mut ation in the LPL gene of proband KD was newly characterized as a nucle otide C-972 to A transversion in exon 6, resulting in substitution of a premature termination codon (TGA) for Cys(239) (TGC). This nonsense mutation, designated as LPL(obama), creates an MboI restriction site a nd eliminates an HgiAI restriction site, and this allows rapid screeni ng of subjects with type IV as well as type I hyperlipoproteinemia for the mutation. The homozygous state for the LPL(obama) allele resulted in neither detectable LPL activity nor immunoreactive LPL mass in PHP , and this was seen in two of proband KD's siblings.