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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). 1993

S Haubenwallner, and G Hörl, and N S Shachter, and E Presta, and S K Fried, and G Höfler, and G M Kostner, and J L Breslow, and R Zechner
Institute of Medical Biochemistry, Karl-Franzens University Graz, Austria.

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.

UI MeSH Term Description Entries
D008071 Lipoprotein Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. Heparin-Clearing Factor,Lipemia-Clearing Factor,Diacylglycerol Lipase,Diglyceride Lipase,Post-Heparin Lipase,Postheparin Lipase,Postheparin Lipoprotein Lipase,Factor, Heparin-Clearing,Factor, Lipemia-Clearing,Heparin Clearing Factor,Lipase, Diacylglycerol,Lipase, Diglyceride,Lipase, Lipoprotein,Lipase, Post-Heparin,Lipase, Postheparin,Lipase, Postheparin Lipoprotein,Lipemia Clearing Factor,Lipoprotein Lipase, Postheparin,Post Heparin Lipase
D008072 Hyperlipoproteinemia Type I An inherited condition due to a deficiency of either LIPOPROTEIN LIPASE or APOLIPOPROTEIN C-II (a lipase-activating protein). The lack of lipase activities results in inability to remove CHYLOMICRONS and TRIGLYCERIDES from the blood which has a creamy top layer after standing. Apolipoprotein C-II Deficiency,Hyperchylomicronemia, Familial,Lipoprotein Lipase Deficiency, Familial,Burger-Grutz Syndrome,C-II Anapolipoproteinemia,Chylomicronemia, Familial,Familial Fat-Induced Hypertriglyceridemia,Familial Hyperchylomicronemia,Familial Hyperlipoproteinemia Type 1,Familial LPL Deficiency,Familial Lipoprotein Lipase Deficiency,Hyperlipemia, Essential Familial,Hyperlipemia, Idiopathic, Burger-Grutz Type,Hyperlipoproteinemia Type Ia,Hyperlipoproteinemia Type Ib,Hyperlipoproteinemia, Type I,Hyperlipoproteinemia, Type Ia,Hyperlipoproteinemia, Type Ib,LIPD Deficiency,Lipase D Deficiency,Lipoprotein Lipase Deficiency,Anapolipoproteinemia, C-II,Anapolipoproteinemias, C-II,Apolipoprotein C II Deficiency,Apolipoprotein C-II Deficiencies,Burger Grutz Syndrome,Burger-Grutz Syndromes,C-II Anapolipoproteinemias,Chylomicronemias, Familial,Deficiencies, Apolipoprotein C-II,Deficiencies, Familial LPL,Deficiencies, LIPD,Deficiencies, Lipase D,Deficiencies, Lipoprotein Lipase,Deficiency, Apolipoprotein C-II,Deficiency, Familial LPL,Deficiency, LIPD,Deficiency, Lipase D,Deficiency, Lipoprotein Lipase,Essential Familial Hyperlipemia,Essential Familial Hyperlipemias,Familial Chylomicronemia,Familial Chylomicronemias,Familial Fat Induced Hypertriglyceridemia,Familial Fat-Induced Hypertriglyceridemias,Familial Hyperchylomicronemias,Familial Hyperlipemia, Essential,Familial Hyperlipemias, Essential,Familial LPL Deficiencies,Fat-Induced Hypertriglyceridemia, Familial,Fat-Induced Hypertriglyceridemias, Familial,Hyperchylomicronemias, Familial,Hyperlipemias, Essential Familial,Hyperlipoproteinemia Type Ias,Hyperlipoproteinemia Type Ibs,Hyperlipoproteinemia Type Is,Hyperlipoproteinemias, Type I,Hyperlipoproteinemias, Type Ia,Hyperlipoproteinemias, Type Ib,Hypertriglyceridemia, Familial Fat-Induced,Hypertriglyceridemias, Familial Fat-Induced,LIPD Deficiencies,LPL Deficiencies, Familial,LPL Deficiency, Familial,Lipase D Deficiencies,Lipase Deficiencies, Lipoprotein,Lipoprotein Lipase Deficiencies,Syndrome, Burger-Grutz,Syndromes, Burger-Grutz,Type I Hyperlipoproteinemia,Type I Hyperlipoproteinemias,Type Ia Hyperlipoproteinemia,Type Ia Hyperlipoproteinemias,Type Ib Hyperlipoproteinemia,Type Ib Hyperlipoproteinemias
D008297 Male Males
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010375 Pedigree The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition. Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005091 Exons The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA. Mini-Exon,Exon,Mini Exon,Mini-Exons
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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