title: New methods for rapid detection of low-density lipoprotein receptor and apolipoprotein B gene mutations causing familial hypercholesterolemia.
abstract: Due to a genetic founder effect, five mutations in the low-density lipoprotein receptor gene account for approximately 83% of familial hypercholesterolemia (FH) diagnosed in French-Canadians. The most frequent mutation, present in 61% of heterozygotes, is a > 10 kb deletion of the 5' region of the gene that removes the promoter and the first exon, resulting in a null allele. Other less prevalent mutations include a gene deletion of approximately 5 kb, which removes exons 2 and 3 (2% of cases) and three missense mutations: Trp66-->Gly (exon 3) (12%), Glu207-->Lys (exon 4) (3%), and Cys646-->Tyr (exon 14) (6%). The apoB Arg3500-->Gln mutation was absent in 228 French Canadians with the FH phenotype. Taking advantage of the availability of fluorescent DNA detection, we have substantially improved the assays for these mutations.
authors.affiliation: Department of Hyperlipidemia and Atherosclerosis, Clinical Research Institute of Montreal, P.Q. Canada.
authors.forename: A
authors.initials: A
authors.lastname: Minnich
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: A
authors.initials: A
authors.lastname: Chamberland
authors.forename: J
authors.initials: J
authors.lastname: Lavigne
authors.forename: J
authors.initials: J
authors.lastname: Davignon
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D004247:DNA / Q000032:analysis*; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D001055:Apolipoproteins B; D011973:Receptors, LDL; D004247:DNA