title: Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries.
abstract: Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg243His mutation while the patients of German and French descent have a novel Arg243Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg243Cys substitution which together with the Arg243His mutation would implicate three recurrent mutations involving the first and second nucleotides of the codon encoding Arg243 of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: M S
authors.initials: MS
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
authors.forename: T
authors.initials: T
authors.lastname: Bruin
authors.forename: U
authors.initials: U
authors.lastname: Beisiegel
authors.forename: P
authors.initials: P
authors.lastname: Benlian
authors.forename: L
authors.initials: L
authors.lastname: Foubert
authors.forename: J L
authors.initials: JL
authors.lastname: De Gennes
authors.forename: H
authors.initials: H
authors.lastname: Funke
authors.forename: I
authors.initials: I
authors.lastname: Forsythe
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001120:Arginine / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002675:Child, Preschool; D002681:China; D005060:Europe; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000208:ethnology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D001120:Arginine; D008071:Lipoprotein Lipase