A new lipoprotein lipase gene mutation discovered in a family with hypertriglyceridemia

Introduction Hypertriglyceridemia (HTG) is a common lipid disorder associated with increased risk of acute pancreatitis and cardiovascular disease (CVD). This study aimed to characterize a pedigree with familial aggregation of HTG and investigate the potential contribution of a novel variant in the lipoprotein lipase (*LPL*) gene. Methods We performed whole exome sequencing (WES) on the proband, who was first diagnosed with severe HTG at 26 years of age. The identified variant was subsequently validated by Sanger sequencing using genomic DNA from the proband and available family members. Genotype–phenotype analysis and in vitro functional assays were performed to evaluate its potential contribution to HTG. Results We identified a novel heterozygous *LPL* c.827T>C (p.I276T) variant in the proband. HTG was enriched among *LPL* p.I276T carriers. In vitro functional assays showed that p.I276T did not significantly affect basal *LPL* mRNA abundance or intracellular protein levels but impaired heparin-mediated LPL release and reduced total catalytic activity. Conclusion This study identified and functionally characterized a novel heterozygous *LPL* p.I276T variant in a pedigree with familial aggregation of HTG. Our findings suggest that this variant may act as a genetic modifier of HTG susceptibility in this pedigree.