Abstract
Objective: Autosomal dominant hypercholesterolemias are due to defects in the LDL receptor (LDLR) gene, in the apolipoprotein B-100 gene or in the proprotein convertase subtilisin/kexin type 9 gene. The aim of this study was to identify and functionally characterize mutations in the LDLR gene that account for most cases of familial hypercholesterolemia (FH). Methods: We enrolled 56 unrelated patients from Southern Italy with a clinical diagnosis of FH. The mutation screening was performed by direct sequencing of the promoter and the 18 exons of the LDLR gene and by multiplex ligation-dependent probe amplification (MLPA) analysis to search for large rearrangements. Results and conclusion: We found 5 new mutations, the causative role of which was demonstrated by functional characterization performed by quantification of fluorescent LDL uptake in EBV-transformed B lymphocytes. These results enlarge the spectrum of FH-causative LDLR mutations. Lastly, screening for large rearrangements is highly recommended for the genetic diagnosis of FH.
Original language | English |
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Pages (from-to) | 493-496 |
Number of pages | 4 |
Journal | Atherosclerosis |
Volume | 210 |
Issue number | 2 |
DOIs | |
Publication status | Published - Jun 2010 |
Keywords
- Familial hypercholesterolemia
- Large rearrangements
- LDL receptor
- LDL uptake assay
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine