Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene

Claudio Rabacchi, Sergio D'Addato, Silvia Palmisano, Tiziano Lucchi, Stefano Bertolini, Sebastiano Calandra, Patrizia Tarugi

Research output: Contribution to journalArticlepeer-review


Background: 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). Methods: We sequenced the familial chylomicronemia candidate genes in 2 adult females presenting long-standing hypertriglyceridemia and a history of acute pancreatitis. Results: Both probands had plasma triglyceride >10 mmol/L but no mutations in the . LPL gene. The sequence of the other candidate genes showed that one patient was homozygous for a novel missense mutation p.(Cys83Arg), and the other was homozygous for a previously reported nonsense mutation p.(Cys 89*), respectively, in GPIHBP1. Family screening showed that the hypertriglyceridemic brother of the p.(Cys83Arg) homozygote was also homozygous for this mutation. He had no history of pancreatitis. The p.(Cys83Arg) heterozygous carriers had normal triglyceride levels. The substitution of a cysteine residue in the Ly6 domain of GPIHBP1 is predicted to abolish one of the disulfide bridges required to maintain the structure of GPIHBP1. The p.(Cys89*) mutation results in a truncated protein devoid of function. Conclusions: Both mutant GPIHBP1 proteins are expected to be incapable of transferring LPL from the subendothelial space to the endothelial surface.

Original languageEnglish
JournalJournal of Clinical Lipidology
Publication statusAccepted/In press - Jan 18 2016


  • Familial chylomicronemia
  • Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1)
  • Hypertriglyceridemia
  • Pancreatitis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics


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