title: A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries.
abstract: Lipoprotein lipase (LPL) plays a crucial role in the regulation of lipoprotein metabolism by hydrolysing the core triglycerides of circulating chylomicrons and VLDL. Human, bovine, mouse, and guinea pig complementary DNA clones have recently been isolated and the organization of the human LPL gene is now known to comprise 10 exons spanning approximately 30 kb. Here we report a similar mutation on 21 alleles from 13 unrelated affected probands with LPL deficiency of French Canadian, English, Polish, German, Dutch, and East Indian ancestry. We show that an identical missense mutation within exon 5, resulting in an amino acid substitution of glutamic acid for glycine at position 188, is responsible for LPL deficiency in 21 of 88 LPL alleles assessed. This mutation alters an Ava II restriction site in exon 5 and will allow a rapid screening test for this mutation in patients with LPL deficiency. This mutation has occurred on the same haplotype in all the unrelated affected persons suggesting a common origin. The amino acid substitution lies within the longest segment of homology for LPL in different species and results in a protein that is catalytically defective.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: M V
authors.initials: MV
authors.lastname: Monsalve
authors.forename: H
authors.initials: H
authors.lastname: Henderson
authors.forename: G
authors.initials: G
authors.lastname: Roederer
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: S
authors.initials: S
authors.lastname: Deeb
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: L
authors.initials: L
authors.lastname: Peritz
authors.forename: R
authors.initials: R
authors.lastname: Devlin
authors.forename: T
authors.initials: T
authors.lastname: Bruin
authors.forename: M R
authors.initials: MR
authors.lastname: Murthy
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005091:Exons; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013329:Structure-Activity Relationship
chemical_list: D009841:Oligonucleotides; D008071:Lipoprotein Lipase