title: The familial hypercholesterolemia (FH)-North Karelia mutation of the low density lipoprotein receptor gene deletes seven nucleotides of exon 6 and is a common cause of FH in Finland.
abstract: A mutation of the LDL receptor gene very common among Finnish patients with heterozygous familial hypercholesterolemia (FH) was identified. This mutation, designated as FH-North Karelia, deletes seven nucleotides from exon 6 of the LDL receptor gene, causes a translational frameshift, and is predicted to result in a truncated receptor protein. Only minute quantities of mRNA corresponding to the deleted gene were detected. Functional studies using cultured fibroblasts from the patients revealed that the FH-North Karelia gene is associated with a receptor-negative (or binding-defective) phenotype of FH. Carriers of the FH-North Karelia gene showed a typical xanthomatous form of FH, with mean serum total and LDL cholesterol levels of 12 and 10 mmol/liter, respectively. This mutation was found in 69 (34%) out of 201 nonrelated Finnish FH patients and was especially abundant (prevalence 79%) in patients from the eastern Finland. These results, combined with our earlier data on another LDL receptor gene deletion (FH-Helsinki), demonstrate that two "Finnish-type" mutant LDL receptor genes make up about two thirds of FH mutations in this country, reflecting a founder gene effect. This background provides good possibilities to examine whether genetic heterogeneity affects the clinical presentation or responsiveness to therapeutic interventions in FH.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: U M
authors.initials: UM
authors.lastname: Koivisto
authors.forename: H
authors.initials: H
authors.lastname: Turtola
authors.forename: K
authors.initials: K
authors.lastname: Aalto-Setälä
authors.forename: B
authors.initials: B
authors.lastname: Top
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
authors.forename: P T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: A C
authors.initials: AC
authors.lastname: Syvänen
authors.forename: K
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D005091:Exons; D005387:Finland; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000209:etiology / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL