目的: Familial chylomicronemia is a recessive disorder that may be due to mutations in lipoprotein lipase (LPL) and in other proteins such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface), and LMF1 (a factor required for intracellular formation of active LPL).The aim of this study was to identify novel mutations in the LPL gene causing familial chylomicronemia and hypertriglyceridemia acute pancreatitis.
 

方法: We sequenced the familial chylomicronemia candidate genes in 2 adult female probands presenting long-standing hypertriglyceridemia and a history of acute pancreatitis in their pregnancy.
 

结果: Both probands had plasma triglyceride >10 mmol/L and four same mutations in the LPL gene. The sequence results showed that the four novel heterozygosis SNPs were composed of two missense SNPs, one synonymous SNP, and one nonsense SNP. The SNPs were c. G829A (p.Asp277Asn); c. T904C(p.Cys302Arg); c.C1164A(p.388Thr); and c.C1421G(p.S474*). Both probands had hypertriglyceridemia acute pancreatitis in their pregnancy. Pre-heparin and post-heparin plasma of the two probands were also used for LPL enzymatic activity detection. And, the results showed a remarkable reduction of LPL enzymatic activity in two probands. By the way, we also sequenced these genes in theirs second sister, who had no history of chylomicronemia or hypertriglyceridemia acute pancreatitis. The results showed that these four SNPs were not found in this second sister.
 

结论: We concluded that these four novel mutations caused chylomicronemia and  hypertriglyceridemia acute pancreatitis by inducing a reduction in LPL enzymatic activity.