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Spectrum of low density lipoprotein receptor mutations in Czech hypercholesterolemic patients
Author(s) -
Kuhrová Viera,
Francová Hana,
Zapletalová Petra,
Freiberger Tomáš,
Fajkusová Lenka,
Hrabincová Eva,
Slováková Romana,
Kozák Libor
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9000
Subject(s) - heteroduplex , biology , genetics , missense mutation , ldl receptor , single strand conformation polymorphism , nonsense mutation , coding region , familial hypercholesterolemia , gene , mutation , point mutation , exon , microbiology and biotechnology , lipoprotein , cholesterol , endocrinology
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. © 2001 Wiley‐Liss, Inc.