FH-Pyrgos: a novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia.

Abstract

In a patient with familial hypercholesterolemia (FH), we have identified a new mutation (-45delT) in repeat 3 of the low-density lipoprotein receptor (LDLR) gene promoter. Analysis of a neutral polymorphism in the LDLR mRNA from the patient's white blood cells showed that the expression of one allele was significantly reduced, and cells have only 24% of LDLR activity by binding and uptake of DiI-LDL. Transient transfection studies using a luciferase gene reporter revealed that the -45delT mutation considerably reduces the transcriptional activity of the LDLR promoter and strongly suggest that the mutation is the cause of the FH phenotype.

• Authors: G V Z Dedoussis, C Pitsavos, D Kelberman, J Skoumas, M E Prassa, D M Choumerianou, C Stefanadis, S E Humphries, P Toutouzas
• Journal: Clinical genetics (Clin Genet) Vol. 64 Issue 5 Pg. 414-9 (Nov 2003) ISSN: 0009-9163 [Print] Denmark
• PMID: 14616764 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, LDL

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Base Sequence
• Female
• Gene Expression
• Humans
• Hyperlipoproteinemia Type II (genetics)
• Male
• Middle Aged
• Molecular Sequence Data
• Mutation
• Pedigree
• Polymorphism, Genetic
• Promoter Regions, Genetic
• Receptors, LDL (genetics)