title: A missense mutation (Asp250----Asn) in exon 6 of the human lipoprotein lipase gene causes chylomicronemia in patients of different ancestries.
abstract: We have previously reported two common lipoprotein lipase (LPL) gene mutations underlying LPL deficiency in the majority of 37 French Canadians (Monsalve et al., 1990. J. Clin. Invest. 86: 728-734; Ma et al., 1991. N. Engl. J. Med. 324: 1761-1766). By examining the 10 coding exons of the LPL gene in another French Canadian patient, we have identified a third missense mutation that is found in two of the three remaining patients for whom mutations are undefined. This is a G to A transition in exon 6 that results in a substitution of asparagine for aspartic acid at residue 250. Using in vitro site-directed mutagenesis, we have confirmed that this mutation causes a catalytically defective LPL protein. In addition, the Asp250----Asn mutation was also found on the same haplotype in an LPL-deficient patient of Dutch ancestry, suggesting a common origin. This mutation alters a TaqI restriction site in exon 6 and will allow for rapid screening in patients with LPL deficiency.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: B I
authors.initials: BI
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Bijvoet
authors.forename: H E
authors.initials: HE
authors.lastname: Henderson
authors.forename: E
authors.initials: E
authors.lastname: Cramb
authors.forename: G
authors.initials: G
authors.lastname: Roederer
authors.forename: M R
authors.initials: MR
authors.lastname: Ven Murthy
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: H D
authors.initials: HD
authors.lastname: Bakker
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002170:Canada; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity; D005091:Exons; D005260:Female; D005602:France / Q000208:ethnology; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009426:Netherlands; D010375:Pedigree
chemical_list: D004247:DNA; D008071:Lipoprotein Lipase