title: A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis.
abstract: A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.
authors.affiliation: Department of Pathophysiology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xue-Hui
authors.initials: XH
authors.lastname: Yu
authors.forename: Tie-Qiang
authors.initials: TQ
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zhao-Ping
authors.initials: ZP
authors.lastname: Liu
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D018387:Codon, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics*; D006953:Hyperlipoproteinemia Type IV / Q000201:enzymology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics; D012008:Recurrence
chemical_list: D018387:Codon, Initiator; D008071:Lipoprotein Lipase