Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene.

D Ameis; J Kobayashi; R C Davis; O Ben-Zeev; M J Malloy; J P Kane; G Lee; H Wong; R J Havel; M C Schotz

doi:10.1172/JCI115114

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Ameis, D. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Kobayashi, J. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Davis, R. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Ben-Zeev, O. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Malloy, M. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Kane, J. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Lee, G. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Wong, H. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Havel, R. in: PubMed | Google Scholar

Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Find articles by Schotz, M. in: PubMed | Google Scholar

Published in Volume 87, Issue 4 on April 1, 1991
J Clin Invest. 1991;87(4):1165–1170. https://doi.org/10.1172/JCI115114.
© 1991 The American Society for Clinical Investigation

Published April 1, 1991 - Version history

Complete deficiency of lipoprotein lipase (LPL) causes the chylomicronemia syndrome. To understand the molecular basis of LPL deficiency, two siblings with drastically reduced postheparin plasma lipolytic activities were selected for analysis of their LPL gene. We used the polymerase chain reaction to examine the nine coding LPL exons in the two affected siblings and three relatives. DNA sequence analysis revealed a single nucleotide change compared with the normal LPL cDNA: a G----A substitution at nucleotide position 680. This transition caused a replacement of glutamic acid for glycine at amino acid residue 142 of the mature LPL protein. Amino acid sequence comparisons of the region surrounding glycine-142 indicated that it is highly conserved among lipases from different species, suggesting a crucial role of this domain for the LPL structure. Expression studies of the mutant LPL cDNA in COS-7 cells produced normal amounts of enzyme mass. However, the mutated LPL was not catalytically active, nor was it efficiently secreted from the cells. This established that the Gly----Glu substitution at amino acid 142 is sufficient to abolish enzymatic activity and to result in the chylomicronemia syndrome observed in these patients.

Images.

Version 1 (April 1, 1991): No description

Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene.

D Ameis, J Kobayashi, R C Davis, O Ben-Zeev, M J Malloy, J P Kane, G Lee, H Wong, R J Havel, and M C Schotz

Article tools

Metrics

Go to

Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene.

D Ameis, J Kobayashi, R C Davis, O Ben-Zeev, M J Malloy, J P Kane, G Lee, H Wong, R J Havel, and M C Schotz

Article tools

Metrics

Go to

Sign up for email alerts