title: A 3-day-old neonate with severe hypertriglyceridemia from novel mutations of the GPIHBP1 gene.
abstract: BACKGROUND
  Familial chylomicronemia is a genetic defect of the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Intravascular lipolysis involves the TG-hydrolase lipoprotein lipase (LPL) as well as other factors such as apolipoprotein CII and apolipoprotein AV (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 a neonate with chylomicronemia.
  
  
  RESULTS
  A 3-day-old newborn was found to have chylomicronemia (plasma TG 18.8 mmol/L, 1.667 mg/dL). The discontinuation of breastfeeding for 24 hours reduced plasma TG to 2.3 mmol/L (201 mg/dL), whereas its resumption induced a sharp TG increase (7.9 mmol/L, 690 mg/dL). The child was switched to a low-fat diet, which was effective in maintaining TG level below 3.5 mmol/L (294 mg/dL) during the first months of life. The child was found to be a compound heterozygous for 2 novel mutations in GPIHBP1 gene. The first mutation was a 9-bp deletion and 4-bp insertion in exon 2, causing a frameshift that abolished the canonical termination codon TGA. The predicted translation product of the mutant messenger RNA is a peptide that contains 51 amino acids of the N-terminal end of the wild-type protein followed by 252 novel amino acids. The second mutation was a nucleotide change (c.319T>C), causing an amino acid substitution p.(Ser107Pro) predicted in silico to be damaging.
  
  
  CONCLUSIONS
  GPIHBP1 mutations should be considered in neonates with chylomicronemia negative for mutations in LPL gene.
authors.affiliation: Rare Diseases and Medical Genetics, Bambino Gesù Children Hospital, Rome, Italy.
authors.forename: Paola Sabrina
authors.initials: PS
authors.lastname: Buonuomo
authors.affiliation: Rare Diseases and Medical Genetics, Bambino Gesù Children Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bartuli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.affiliation: Department of Internal Medicine, University of Genova, Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: sebcal@unimore.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
mesh_terms: D056726:Genetic Association Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D007231:Infant, Newborn; D008071:Lipoprotein Lipase / Q000235:genetics; D009154:Mutation; D018110:Receptors, Lipoprotein / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase
keywords: (GPIHBP1) glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1; Hypertriglyceridemia; Intravascular lipolysis; Lipoprotein lipase