title: Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.
abstract: BACKGROUND
  Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X).
  
  
  OBJECTIVE
  The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded.
  
  
  RESULTS
  The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and recurrent episodes of pancreatitis. The mutation causes a G>A substitution in exon 9 (c.1395G>A), leading to a premature stop codon (W464X). LPL activity and mass were reduced by 76 and 50%, respectively, compared with normolipidemic controls. The proband over the years has shown a good response to treatment. The proband's son, heterozygous for the W464X, shows normal plasma triglyceride levels.
  
  
  CONCLUSIONS
  We identified the second novel pathogenic mutation in LMF1 gene in a patient with severe hypertriglyceridemia. LPL deficiency in our patient was milder than in the carrier of the Y439X previously described.
authors.affiliation: Department of Clinical Medicine and Emerging Diseases, University of Palermo, 90127 Palermo, Italy.
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Arpi
authors.forename: Fen
authors.initials: F
authors.lastname: Yin
authors.forename: Rossella
authors.initials: R
authors.lastname: Spina
authors.forename: Hannele
authors.initials: H
authors.lastname: Hilden
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Barbagallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Carroccio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Squatrito
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vigneri
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Miklós
authors.initials: M
authors.lastname: Péterfy
authors.forename: Maurizio R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000328:Adult; D001483:Base Sequence; D018389:Codon, Nonsense; D015248:Gemfibrozil / Q000627:therapeutic use; D014644:Genetic Variation; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D014280:Triglycerides / Q000097:blood
chemical_list: D018389:Codon, Nonsense; D000960:Hypolipidemic Agents; D014280:Triglycerides; D008071:Lipoprotein Lipase; D015248:Gemfibrozil