Journal of Lipid Research, Vol 35, 220-228, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

A novel amino acid substitution (His183-->Gln) in exon 5 of the lipoprotein lipase gene results in loss of catalytic activity: phenotypic expression of the mutant gene in a heterozygous state

H Tenkanen, MR Taskinen, M Antikainen, I Ulmanen, K Kontula and C Ehnholm
National Public Health Institute, University of Helsinki, Finland.

We have identified a hitherto unrecognized mutation of the lipoprotein lipase gene (LPL) in a Finnish family with Russian and Swiss ancestors. A single base pair substitution of a guanine for cytosine in codon 183 of exon 5 of the LPL gene results in a change of histidine to glutamine in the mature enzyme protein. Expression of a mutant cDNA construct in COS cells resulted in secretion of inactive LPL enzyme protein confirming the functional significance of the mutation. The proband, a 50-year-old female and her two daughters were all heterozygous for the His183-->Gln mutation. Clinically, the proband was characterized by variable and occasionally severe hypertriglyceridemia, obesity, hypertension, coronary heart disease and non-insulin-dependent diabetes mellitus. The daughters, aged 24 and 19 years, were also obese but had milder hypertriglyceridemia. In conclusion, we have identified a novel LPL mutation that results in the synthesis of an inactive enzyme protein. Although the assessment of a causative link between the mutation and hyperlipidemia awaits further studies, our data suggest that heterozygosity for a functional defect of LPL should be considered in patients presenting with the metabolic dyslipidemic syndrome, "syndrome-X."
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