title: A heterozygous mutation (the codon for Ser447----a stop codon) in lipoprotein lipase contributes to a defect in lipid interface recognition in a case with type I hyperlipidemia.
abstract: Previously, we reported a case with type I hyperlipidemia due to a lipid interface recognition deficiency in lipoprotein lipase (LPL) (1). The LPL from postheparin plasma of this patient did not hydrolyze TritonX-100-triolein or very low density lipoprotein-triolein but did hydrolyze tributyrin and LysoPC-triolein substrates. Sequence analysis of the probands DNA revealed a heterozygous nucleotide change: a C----G transversion at position of 1595, resulting in changing the codon for Ser447 to a stop codon. Expression studies of this mutant LPLcDNA in Cos-1 cells produced and secreted considerable amounts of LPL mass in the culture media. The mutated LPL hydrolyzed much less TritonX-100-triolein than wild type LPL, whereas hydrolysis of tributyrin and LysoPC--triolein was the same with both the mutant and wild type LPL. These results suggest that this mutation might be responsible for the property of the LPL with a defect in lipid interface recognition in the type I patient we reported.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Nishida
authors.forename: D
authors.initials: D
authors.lastname: Ameis
authors.forename: G
authors.initials: G
authors.lastname: Stahnke
authors.forename: M C
authors.initials: MC
authors.lastname: Schotz
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: I
authors.initials: I
authors.lastname: Fukamachi
authors.forename: K
authors.initials: K
authors.lastname: Shirai
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012694:Serine
chemical_list: D003062:Codon; D009838:Oligodeoxyribonucleotides; D012694:Serine; D004247:DNA; D008071:Lipoprotein Lipase