title: Identification and functional characterization of LDLR mutations in familial hypercholesterolemia patients from Southern Italy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CEINGE S.C.a r.l. Biotecnologie Avanzate, Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Romano
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Di Taranto
authors.forename: Maria Nicoletta
authors.initials: MN
authors.lastname: D'Agostino
authors.forename: Gennaro
authors.initials: G
authors.lastname: Marotta
authors.forename: Marco
authors.initials: M
authors.lastname: Gentile
authors.forename: Giovanna
authors.initials: G
authors.lastname: Abate
authors.forename: Peppino
authors.initials: P
authors.lastname: Mirabelli
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Noto
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Paolo
authors.initials: P
authors.lastname: Rubba
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fortunato
mesh_terms: D053299:Apolipoprotein B-100 / Q000235:genetics; D053283:Apolipoprotein B-48; D002461:Cell Line, Transformed; D002469:Cell Separation; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009154:Mutation; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D018076:DNA, Complementary; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases