title: Compound heterozygosity for a known and a novel defect in the lipoprotein lipase gene (Asp250-->Asn; Ser251-->Cys) resulting in lipoprotein lipase (LPL) deficiency.
abstract: Two missense mutations in exon 6 of the LPL gene were identified on separate alleles in a Dutch patient with lipoprotein lipase (LPL) deficiency. The first mutation is a G1003-->A transition resulting in a D250N mutation, which has been shown previously to result in a catalytically defective protein in patients of French-Canadian ancestry. The second mutation, a C to G transition at nucleotide 1007, predicts a S251C residue change in the highly conserved region of LPL surrounding the loop structure the covers the catalytic triad. This mutation constitutes a novel defect among LPL gene mutations reported so far. Site-directed mutagenesis experiments provide in-vitro evidence for the complete loss of LPL activity resulting from this latter missense mutation. The G1003-->A nucleotide substitution underlying the Asp250 mutation deletes a TaqI endonuclease recognition site and the C1007-->G change that leads to the S251C alteration abolishes a HinfI recognition site. This will facilitate rapid screening for these mutations in LPL-deficient patients.
authors.affiliation: Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Bijvoet
authors.forename: H
authors.initials: H
authors.lastname: Wiebusch
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: P W
authors.initials: PW
authors.lastname: Reymer
authors.forename: T
authors.initials: T
authors.lastname: Bruin
authors.forename: H D
authors.initials: HD
authors.lastname: Bakker
authors.forename: H
authors.initials: H
authors.lastname: Funke
authors.forename: G
authors.initials: G
authors.lastname: Assmann
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000293:Adolescent; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004247:DNA / Q000032:analysis; D003718:Denmark; D006579:Heterozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000235:genetics*; D015228:Hypertriglyceridemia / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics*; D008297:Male; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012694:Serine / Q000235:genetics
chemical_list: D001224:Aspartic Acid; D012694:Serine; D001216:Asparagine; D004247:DNA; D008071:Lipoprotein Lipase; D003545:Cysteine