title: A missense mutation (Trp86----Arg) in exon 3 of the lipoprotein lipase gene: a cause of familial chylomicronemia.
abstract: We have investigated a patient of English ancestry with familial chylomicronemia caused by lipoprotein lipase (LPL) deficiency. DNA sequence analysis of all exons and intron-exon boundaries of the LPL gene identified two single-base mutations, a T----C transition for codon 86 (TGG) at nucleotide 511, resulting in a Trp86----Arg substitution, and a C----T transition at nucleotide 571, involving the codon CAG encoding Gln106 and producing Gln106----Stop, a mutation described by Emi et al. The functional significance of the two mutations was confirmed by in vitro expression and enzyme activity assays of the mutant LPL. Linkage analysis established that the patient is a compound heterozygote for the two mutations. The Trp86----Arg mutation in exon 3 is the first natural mutation identified outside exons 4-6, which encompass the catalytic triad residues.
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: K
authors.initials: K
authors.lastname: Ishimura-Oka
authors.forename: F
authors.initials: F
authors.lastname: Faustinella
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: L C
authors.initials: LC
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Oka
authors.forename: L
authors.initials: L
authors.lastname: Chan
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D001483:Base Sequence; D002914:Chylomicrons / Q000097:blood*; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics*; D007438:Introns; D008071:Lipoprotein Lipase / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D015183:Restriction Mapping; D014364:Tryptophan
chemical_list: D002914:Chylomicrons; D003062:Codon; D014364:Tryptophan; D004247:DNA; D001120:Arginine; D008071:Lipoprotein Lipase