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FH‐Pyrgos: a novel mutation in the promoter (−45delT) of the low‐density lipoprotein receptor gene associated with familial hypercholesterolemia
Author(s) -
Dedoussis GVZ,
Pitsavos C,
Kelberman D,
Skoumas J,
Prassa ME,
Choumerianou DM,
Stefanadis C,
Humphries SE,
Toutouzas P
Publication year - 2003
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2003.00164.x
Subject(s) - familial hypercholesterolemia , genetics , ldl receptor , mutation , gene , biology , medicine , lipoprotein , endocrinology , cholesterol
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.