title: Novel LPL mutation (L303F) found in a patient associated with coronary artery disease and severe systemic atherosclerosis.
abstract: BACKGROUND
  Patients with lipoprotein lipase (LPL) deficiency had been generally thought to be spared accelerated atherosclerosis in spite of a marked elevation of plasma triglyceride levels. However, it has been recently reported that some heterozygous and homozygous LPL-deficient patients are associated with premature atherosclerosis. In this paper, we report a 55-year-old type I hyperlipidaemic patient with a novel missense mutation in the LPL gene.
  
  
  RESULTS
  The patient had suffered from coronary artery disease, abdominal aortic aneurysm, and stenoses of the bilateral renal arteries and superficial femoral arteries. Sequencing of the genomic DNA revealed that the patient was a homozygote for the mutation, a G to C transition at nucleotide position 1069 in the exon 6, resulting in an amino acid substitution of Phe for Leu303 (L303F). Approximately 6% and approximately 40% of normal LPL activity and LPL mass, respectively, were detected in the patient's postheparin plasma. An in vitro expression study demonstrated that COS7 cells transfected with L303F mutant cDNA produced a 40% amount of LPL protein in cell lysates compared with normal cDNA, but no protein was detected in the media. Lipoprotein lipase activity was completely absent in both lysates and media of the cells transfected with the mutant cDNA, suggesting that this mutation in the LPL gene results in the production of a functionally inactive protein.
  
  
  CONCLUSIONS
  This case suggests that the LPL missense mutation (L303F), which impairs lipolysis but preserves the LPL mass, is proatherogenic.
authors.affiliation: Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan. naosakai@imed2.med.osaka-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Saika
authors.forename: N
authors.initials: N
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: N
authors.initials: N
authors.lastname: Ouchi
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: H
authors.initials: H
authors.lastname: Hiraoka
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics*; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000150:complications / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D008071:Lipoprotein Lipase