title: Long-distance PCR-based screening for large rearrangements of the LDL receptor gene in Korean patients with familial hypercholesterolemia.
abstract: BACKGROUND
  The LDL receptor is a cell-surface protein that regulates plasma cholesterol by specific uptake of LDL particles from the blood circulation. Familial hypercholesterolemia (FH) results from defective catabolism of LDL, which is caused by mutations in the LDL-receptor gene.
  
  
  METHODS
  For the rapid and reliable detection of large rearrangements in the LDL-receptor gene, we established a screening method based on long-distance PCR as an alternative to Southern-blot hybridization. Using long-distance PCR, 45 unrelated Korean subjects heterozygous for FH were screened to assess the frequency and nature of major structural rearrangements in the LDL-receptor gene.
  
  
  RESULTS
  Two different deletion mutations, FH6 (same type as FH3 and FH311) and FH 32, were detected in four families by long-distance PCR. Detailed restriction mapping and sequence analysis showed that FH6 was a 5.71-kb deletion extending from intron 8 to intron 12 and that FH32 was a 2-kb deletion extending from intron 6 to intron 7. Sequence analysis for the breakpoints of all deletions detected in Korean FH patients showed that only the left arms of the Alu repetitive sequences were involved in the deletion event.
  
  
  CONCLUSIONS
  The screening method based on long-distance PCR provides a powerful strategy for the detection of large rearrangements in the LDL-receptor gene and is a rapid and reliable screening alternative to Southern-blot hybridization.
authors.affiliation: Department of Biology and SRC for Cell Differentiation, Seoul National University, Seoul 151-742, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Bae
authors.forename: J J
authors.initials: JJ
authors.lastname: Chae
authors.forename: U K
authors.initials: UK
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Choe
authors.forename: Y
authors.initials: Y
authors.lastname: Namkoong
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: Y B
authors.initials: YB
authors.lastname: Park
authors.forename: C C
authors.initials: CC
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007723:Korea; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL