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

• Published in: Biochemical and biophysical research communications Vol. 341; no. 1; pp. 82 - 87
• Main Authors: Yu, Xue-Hui, Zhao, Tie-Qiang, Wang, Li, Liu, Zhao-Ping, Zhang, Cheng-Mei, Chen, Rong, Li, Li, Liu, George, Hu, Wei-Cheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.03.2006
• Subjects: Adolescent; Codon, Initiator - genetics; DNA Mutational Analysis; DNA sequencing; Expression analysis; Gene mutation; Humans; Hyperlipoproteinemia Type I - enzymology; Hyperlipoproteinemia Type I - genetics; Hyperlipoproteinemia Type IV - enzymology; Hyperlipoproteinemia Type IV - genetics; Initiation codon; Lipoprotein Lipase - deficiency; Lipoprotein Lipase - genetics; Mutation; Pancreatitis - enzymology; Pancreatitis - genetics; Polymerase chain reaction-single-strand conformation polymorphism; Protein Biosynthesis - genetics; Recurrence; Expression analysis; Lipoprotein lipase deficiency; Polymerase chain reaction-single-strand conformation polymorphism; Gene mutation; Initiation codon; DNA sequencing
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.12.165

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.