title: Clinical and genetic features of 3 patients with familial chylomicronemia due to mutations in GPIHBP1 gene.
abstract: 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).
  
  
  
  We sequenced the familial chylomicronemia candidate genes in 2 adult females presenting long-standing hypertriglyceridemia and a history of acute pancreatitis.
  
  
  
  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.
  
  
  
  Both mutant GPIHBP1 proteins are expected to be incapable of transferring LPL from the subendothelial space to the endothelial surface.
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors: Claudio
authors: C
authors: Rabacchi
authors: Department of Medical and Surgical Sciences, University of Bologna, Italy.
authors: Sergio
authors: S
authors: D'Addato
authors: Department of Medical and Surgical Sciences, University of Bologna, Italy.
authors: Silvia
authors: S
authors: Palmisano
authors: Department of Internal Medicine and Medical Specialities, IRCSS Ca' Granda, Milano, Italy.
authors: Tiziano
authors: T
authors: Lucchi
authors: Department of Internal Medicine, University of Genova, Italy.
authors: Stefano
authors: S
authors: Bertolini
authors: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy.
authors: Sebastiano
authors: S
authors: Calandra
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Italy. Electronic address: tarugi@unimore.it.
authors: Patrizia
authors: P
authors: Tarugi
mesh_terms: D000328:Adult; D001483:Base Sequence; D018389:Codon, Nonsense; D005260:Female; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000175:diagnosis / Q000235:genetics*; D033162:Incidental Findings; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D000072417:Protein Domains; D018110:Receptors, Lipoprotein / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein
keywords: Familial chylomicronemia; Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1); Hypertriglyceridemia; Pancreatitis