title: Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia.
abstract: BACKGROUND
  Monogenic hypertriglyceridemia (HTG) may result from mutations in some genes which impair the intravascular lipolysis of triglyceride (TG)-rich lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia) with recessive transmission.
  
  
  METHODS
  The LPL gene was resequenced in 149 patients with severe HTG (TG > 10 mmol/L) and 106 patients with moderate HTG (TG > 4.5 and <10 mmol/L) referred to tertiary Lipid Clinics in Italy.
  
  
  RESULTS
  In the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%) were compound heterozygotes and 15 patients (10%) were simple heterozygotes for rare LPL gene variants. Single or multiple episodes of pancreatitis were recorded in 24 (48%) of these patients. There was no difference in plasma TG concentration between patients with or without a positive history of pancreatitis. Among moderate HTG patients, six patients (5.6%) were heterozygotes for rare LPL variants; two of them had suffered from pancreatitis. Overall 36 rare LPL variants were found, 15 of which not reported previously. Systematic analysis of close relatives of mutation carriers led to the identification of 44 simple heterozygotes (plasma TG 3.2 ± 4.1 mmol/L), none of whom had a positive history of pancreatitis.
  
  
  CONCLUSIONS
  The prevalence of rare LPL variants in patients with severe or moderate HTG, referred to tertiary lipid clinics, was 50/149 (33.5%) and 6/106 (5.6%), respectively. Systematic analysis of relatives of mutation carriers is an efficient way to identify heterozygotes who may develop severe HTG.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rabacchi
authors.affiliation: Department of Internal Medicine, University of Genova, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.affiliation: Department of Internal Medicine and Medical Specialities, University of Palermo, Italy.
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.affiliation: Department of Internal Medicine and Medical Specialities, University of Palermo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.affiliation: Department of Internal Medicine, University of Genova, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fresa
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.affiliation: Department of Internal Medicine and Medical Specialities, University of Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.affiliation: Department of Internal Medicine, University of Genova, Italy. Electronic address: stefbert@unige.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy. Electronic address: sebcal@unimore.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D007223:Infant; D007558:Italy; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014280:Triglycerides; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: Familial chylomicronemia; Gene variants; Lipoprotein lipase; Pancreatitis; Primary hypertriglyceridemia