Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis

•We studied 2 patients with recurrent pancreatitis and severe hypertriglyceridemia.•Patients exhibited low lipoprotein lipase activity but no rare variants in this gene.•We identified 2 novel missense mutations in the GPIHBP1 gene.•One patient was homozygous for the mutation c.239 C>A, ACG>AAG, p.Thr80>Lys.•The other patient was homozygous for the mutation c.3 G>T, ATG>ATT, p.Met1>Ile.

BackgroundGlycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients.MethodsTwo unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1.ResultsThe 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile).ConclusionIn conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia.