FH-Pyrgos: a novel mutation in the promoter (-45delT) of the low-density lipoprotein receptor gene associated with familial hypercholesterolemia.
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.
Dedoussis
G V Z
GV
Laboratory of Molecular Biology, Department of Science of Dietetics-Nutrition, Harokopio University of Athens, Greece. dedousi@hua.gr
Pitsavos
C
C
Kelberman
D
D
Skoumas
J
J
Prassa
M E
ME
Choumerianou
D M
DM
Stefanadis
C
C
Humphries
S E
SE
Toutouzas
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000235:genetics*
D011973:Receptors, LDL