Low-density lipoprotein receptor (LDLR) is a cell-surface glycoprotein that mediates specific uptake and catabolism of plasma LDL. Mutations located in the coding region of the LDLR gene affect the structure and function of the protein and cause familial hypercholesterolaemia (FH). Mutations in the regulatory regions of the gene are rare, but in some cases have been shown to alter the transcriptional activity of the gene and cause the FH phenotype as well. Adult heterozygous FH individuals have a markedly raised plasma cholesterol that is associated with accelerated atherosclerosis and premature coronary heart disease. The aim of this study was the functional characterization of a promoter mutation in the LDLR gene in one family from the register of Czech FH subjects. Molecular screening revealed that three members of this family carried a -27C > T nucleotide transition in the promoter sequence (calculated from the start of transcription). All three manifested a heterozygous FH phenotype. This new mutation is located between the TATA box and sterol-dependent regulatory element repeat 3. Using a luciferase reporter assay system, we analysed the transcriptional efficiency of the normal and mutant alleles. The mutation reduced promoter activity to background level. Another new promoter mutation -60C > T was identified in an unrelated patient in the conserved nucleotide sequence of the sterol-dependent regulation element repeat 2 which virtually abolished the promoter activity. We assume a causal effect of this -60C > T transition on the basis of its position in the promoter sequence.

• MeSH
• buněčné linie MeSH
• dítě MeSH
• fenotyp MeSH
• heterozygot MeSH
• hyperlipoproteinemie typ II genetika   MeSH
• játra MeSH
• LDL-receptory genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• luciferasy genetika   MeSH
• mladiství MeSH
• mutace * MeSH
• promotorové oblasti (genetika) * MeSH
• sekvence nukleotidů MeSH
• TATA box MeSH
• transfekce MeSH
• Check Tag
• dítě MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• LDL-receptory MeSH
• luciferasy MeSH