title: A mutation in the human lipoprotein lipase gene as the most common cause of familial chylomicronemia in French Canadians.
abstract: BACKGROUND
  Lipoprotein lipase hydrolyzes the triglyceride core of chylomicrons and very-low-density lipoproteins and has a crucial role in regulating plasma lipoprotein levels. Deficiencies of lipoprotein lipase activity lead to aberrations in lipoprotein levels. Worldwide, the frequency of lipoprotein lipase deficiency is highest among French Canadians. We sought to determine the molecular basis of the disorder in this population.
  
  
  METHODS
  The entire coding sequence of the lipoprotein lipase gene from one French Canadian patient was amplified by the polymerase chain reaction and sequenced. Exon 5 from 36 other French Canadian patients was amplified and analyzed by dot blot hybridization with allele-specific oligonucleotides.
  
  
  RESULTS
  Sequence analysis revealed a missense substitution of leucine (CTG) for proline (CCG) at residue 207 in exon 5. This mutation was found on 54 of the 74 mutant alleles (73 percent) in the patients. Studies of site-directed in vitro mutagenesis have confirmed that this mutation generates inactive lipoprotein lipase and is the cause of lipoprotein lipase deficiency.
  
  
  CONCLUSIONS
  We have identified a missense mutation at residue 207 of the lipoprotein lipase gene that is the most common cause of lipoprotein lipase deficiency in French Canadians. This mutation can be easily detected by dot blot analysis, providing opportunity for definitive DNA diagnosis of the disorder and identification of heterozygous carriers.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: H E
authors.initials: HE
authors.lastname: Henderson
authors.forename: V
authors.initials: V
authors.lastname: Murthy
authors.forename: G
authors.initials: G
authors.lastname: Roederer
authors.forename: M V
authors.initials: MV
authors.lastname: Monsalve
authors.forename: L A
authors.initials: LA
authors.lastname: Clarke
authors.forename: T
authors.initials: T
authors.lastname: Normand
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: C
authors.initials: C
authors.lastname: Gagné
authors.forename: M
authors.initials: M
authors.lastname: Lambert
mesh_terms: D001483:Base Sequence; D002170:Canada / Q000453:epidemiology; D002914:Chylomicrons / Q000097:blood*; D004247:DNA / Q000032:analysis; D005602:France / Q000208:ethnology; D006801:Humans; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D009693:Nucleic Acid Hybridization
chemical_list: D002914:Chylomicrons; D004247:DNA; D008071:Lipoprotein Lipase