Identification and functional characterization of LDLR mutations in familial hypercholesterolemia patients from Southern Italy

Maria Romano, Maria Donata Di Taranto, Maria Nicoletta D'Agostino, Gennaro Marotta, Marco Gentile, Giovanna Abate, Peppino Mirabelli, Rosa Di Noto, Luigi Del Vecchio, Paolo Rubba, Giuliana Fortunato

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)493-496
Number of pages4
JournalAtherosclerosis
Volume210
Issue number2
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Familial hypercholesterolemia
  • Large rearrangements
  • LDL receptor
  • LDL uptake assay

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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