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

BACKGROUND: Glycosylphosphatidylinositol-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.
METHODS: Two 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.
RESULTS: The 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).
CONCLUSION: In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated
patients as the cause of their severe hypertriglyceridemia.