A Novel Missense Mutation in the Gene for Lipoprotein Lipase Resulting in a Highly Conservative Amino Acid Substitution (Asp180→Glu) Causes Familial Chylomicronemia (Type I Hyperlipoproteinemia)

G) was detected within exon 5 of the LPL gene in two members of an Italian family affected with type I hyperlipoproteinemia. This mutation causes a highly conservative amino acid replacement (Asp-->Glu) at position 180 of the mature LPL protein resulting in a virtual absence of LPL enzyme activity and LPL enzyme mass in postheparin plasma. Adipose tissue mRNA concentrations and mRNA sizes were not affected. Both patients were homozygous for the mutation, whereas the parents were heterozygous. Comparison of the expression of the mutated cDNA and the wildtype cDNA in cos-7 cells revealed proper transcription and translation of the mutated clone into an immunologically detectable protein. The mutated LPL protein was secreted from the cells in a manner similar to that of wild-type LPL and bound to heparin-Sepharose with identical properties. However, the mutated enzyme, in contrast to wildtype LPL, exhibited no detectable lipolytic activity against a triglyceride substrate. Our results demonstrate that even a highly conservative amino acid replacement outside the proposed active site of LPL is incompatible with proper enzyme function. -->

ISSN:	0888-7543
DOI:	10.1006/geno.1993.1481
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e38cc394fbf17f7a1edc63eb117f7d9e https://doi.org/10.1006/geno.1993.1481
Rights:	OPEN
Přírůstkové číslo:	edsair.doi.dedup.....e38cc394fbf17f7a1edc63eb117f7d9e
Autor:	Jan L. Breslow, Gerald Höfler, Gerd Hörl, Gert M. Kostner, Elio Presta, Neil S. Shachter, Susan K. Fried, Rudolf Zechner, Sabine Haubenwallner
Rok vydání:	1993
Předmět:	Male Molecular Sequence Data Restriction Mapping Gene mutation Biology Conserved sequence Exon Complementary DNA Gene expression Genetics Humans Missense mutation Amino Acid Sequence Peptide sequence Conserved Sequence Lipoprotein lipase Base Sequence nutritional and metabolic diseases DNA Exons Molecular biology Pedigree Lipoprotein Lipase Mutation Female Hyperlipoproteinemia Type I lipids (amino acids peptides and proteins)
Zdroj:	Genomics. 18:392-396
ISSN:	0888-7543
DOI:	10.1006/geno.1993.1481
Popis:	A previously undescribed single missense mutation (C-->G) was detected within exon 5 of the LPL gene in two members of an Italian family affected with type I hyperlipoproteinemia. This mutation causes a highly conservative amino acid replacement (Asp-->Glu) at position 180 of the mature LPL protein resulting in a virtual absence of LPL enzyme activity and LPL enzyme mass in postheparin plasma. Adipose tissue mRNA concentrations and mRNA sizes were not affected. Both patients were homozygous for the mutation, whereas the parents were heterozygous. Comparison of the expression of the mutated cDNA and the wildtype cDNA in cos-7 cells revealed proper transcription and translation of the mutated clone into an immunologically detectable protein. The mutated LPL protein was secreted from the cells in a manner similar to that of wild-type LPL and bound to heparin-Sepharose with identical properties. However, the mutated enzyme, in contrast to wildtype LPL, exhibited no detectable lipolytic activity against a triglyceride substrate. Our results demonstrate that even a highly conservative amino acid replacement outside the proposed active site of LPL is incompatible with proper enzyme function.
Databáze:	OpenAIRE
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