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. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
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. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
Authors: Maria Romano; Maria Donata Di Taranto; Peppino Mirabelli; Maria Nicoletta D'Agostino; Arcangelo Iannuzzi; Gennaro Marotta; Marco Gentile; Maddalena Raia; Rosa Di Noto; Luigi Del Vecchio; Paolo Rubba; Giuliana Fortunato Journal: J Lipid Res Date: 2011-08-24 Impact factor: 5.922
Authors: Asier Benito-Vicente; Kepa B Uribe; Shifa Jebari; Unai Galicia-Garcia; Helena Ostolaza; Cesar Martin Journal: Int J Mol Sci Date: 2018-06-05 Impact factor: 5.923
Authors: Karen H Y Wong; Michal Levy-Sakin; Walfred Ma; Nina Gonzaludo; Angel C Y Mak; Dedeepya Vaka; Annie Poon; Catherine Chu; Richard Lao; Melek Balamir; Zoe Grenville; Nicolas Wong; John P Kane; Pui-Yan Kwok; Mary J Malloy; Clive R Pullinger Journal: Mol Genet Genomic Med Date: 2019-10-16 Impact factor: 2.183