title: Spectrum of low density lipoprotein receptor mutations in Czech hypercholesterolemic patients.
abstract: The aim of our study was to define mutations causing familial hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and PCR/restriction analysis was used for this purpose. Molecular searching in the promoter region and coding sequence of the low density lipoprotein receptor (LDLR) gene in 130 patients from 68 unrelated families resulted in the identification of 37 sequence variations. Thirty of them are most likely disease causing mutations. Nineteen mutations were novel (two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions). Their pathological effect can be predicted on the basis of their position with respect to previously reported mutations with an estimated reduction of the receptor activity and/or premature termination of translation. These results expand our knowledge of mutations responsible for FH. Seven nucleotide variations were characterized as silent polymorphisms. Hum Mutat 18:253, 2001.
authors.affiliation: Research Institute of Child Health, Department of Biochemical and Molecular Genetics, Brno, Czech Republic. vera.kuhrova@volny.cz
authors.forename: V
authors.initials: V
authors.lastname: Kuhrová
authors.forename: H
authors.initials: H
authors.lastname: Francová
authors.forename: P
authors.initials: P
authors.lastname: Zapletalová
authors.forename: T
authors.initials: T
authors.lastname: Freiberger
authors.forename: L
authors.initials: L
authors.lastname: Fajkusová
authors.forename: E
authors.initials: E
authors.lastname: Hrabincová
authors.forename: R
authors.initials: R
authors.lastname: Slováková
authors.forename: L
authors.initials: L
authors.lastname: Kozák
mesh_terms: D000483:Alleles; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018389:Codon, Nonsense; D003604:Czechoslovakia; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D011973:Receptors, LDL / Q000235:genetics*; D017384:Sequence Deletion; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D018389:Codon, Nonsense; D011973:Receptors, LDL; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol