Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis
2016 (English)In: Journal of Clinical Lipidology, ISSN 1933-2874, E-ISSN 1876-4789, Vol. 10, no 1, 92-100 p.Article in journal (Refereed) PublishedText
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 ofGPIHBP1 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.
Place, publisher, year, edition, pages
2016. Vol. 10, no 1, 92-100 p.
Glycosylphosphatidy-linositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), Severe pertriglyceridemia, Recurrent pancreatitis, Lipoprotein lipase activity
IdentifiersURN: urn:nbn:se:umu:diva-118407DOI: 10.1016/j.jacl.2015.09.007ISI: 000370991300009PubMedID: 26892125OAI: oai:DiVA.org:umu-118407DiVA: diva2:918853