title: A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland.
abstract: The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors.
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University, Medical School, Kopernika 15, 31-501, Kraków, Poland. mmwalus@wp.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Waluś-Miarka
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.forename: Barbara
authors.initials: B
authors.lastname: Idzior-Waluś
authors.forename: Przemysław
authors.initials: P
authors.lastname: Miarka
authors.forename: Przemysław
authors.initials: P
authors.lastname: Witek
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Małecki
authors.forename: Danuta
authors.initials: D
authors.lastname: Czarnecka
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D020090:Chromosome Segregation / Q000235:genetics; D004252:DNA Mutational Analysis; D004705:Endocytosis; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011044:Poland; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011485:Protein Binding; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*
chemical_list: C573412:LDLR protein, human; D011973:Receptors, LDL