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.
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.
Yu
Xue-Hui
XH
Department of Pathophysiology, School of Medicine, Shandong University, Jinan, PR China.
Zhao
Tie-Qiang
TQ
Wang
Li
L
Liu
Zhao-Ping
ZP
Zhang
Cheng-Mei
CM
Chen
Rong
R
Li
Li
L
Liu
George
G
Hu
Wei-Cheng
WC
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
D018387:Codon, Initiator; D008071:Lipoprotein Lipase