title: Detection of large deletions in the LDL receptor gene with quantitative PCR methods.
abstract: BACKGROUND
  Familial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations.
  
  
  METHODS
  In this study we tested the ability of two different quantitative PCR methods, i.e. Real-Time PCR and Multiplex Ligation-Dependent Probe Amplification (MLPA), to detect deletions in the LDL receptor gene. We also reassessed the contribution of major structural rearrangements to the mutational spectrum of the LDL receptor gene in Denmark.
  
  
  RESULTS
  With both methods it was possible to discriminate between one and two copies of the LDL receptor gene exon 5, but the MLPA method was cheaper, and it was far more accurate and precise than Real-Time PCR. In five of 318 patients with an FH phenotype, MLPA analysis revealed five different deletions in the LDL receptor gene.
  
  
  CONCLUSIONS
  The MLPA method was accurate, precise and at the same time effective in screening a large number of FH patients for large deletions in the LDL receptor gene.
authors.affiliation: Department of Medicine and Cardiology, Aarhus Sygehus, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. dorte.damgaard@dadlnet.dk
authors.forename: Dorte
authors.initials: D
authors.lastname: Damgaard
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nissen
authors.forename: Lillian G
authors.initials: LG
authors.lastname: Jensen
authors.forename: Gitte G
authors.initials: GG
authors.lastname: Nielsen
authors.forename: Anette
authors.initials: A
authors.lastname: Stenderup
authors.forename: Mogens L
authors.initials: ML
authors.lastname: Larsen
authors.forename: Ole
authors.initials: O
authors.lastname: Faergeman
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods*; D017353:Gene Deletion; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL