Identification and functional characterization of a novel heterozygous missense variant in the LPL associated with recurrent hypertriglyceridemia‐induced acute pancreatitis in pregnancy

Background Acute pancreatitis in pregnancy (APIP) is a life‐threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia‐induced APIP (HTG‐APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency. Methods The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG‐APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells. Results A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. Conclusion This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG‐APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG‐APIP. The present study describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG‐APIP. Our findings not only underscore the importance of genetic defects in predisposing to HTG and/or acute pancreatitis but also shed new light on the complexity underlying the etiology of these phenotypes.