Low-density lipoprotein receptor mutation that deletes exons 2 and 3 by Alu-Alu recombination

J Biochem. 1993 Mar;113(3):372-6. doi: 10.1093/oxfordjournals.jbchem.a124053.

Abstract

A deletion mutant in the low density lipoprotein receptor gene of a Japanese patient with heterozygous familial hypercholesterolemia was analyzed. Genomic Southern blotting showed abnormal size restriction fragments with BamHI (7.8 kb), EcoRI (3.8 kb), BglII (17 kb), KpnI (> 23 kb), EcoRV (13 kb), and XbaI (14 kb). The abnormal EcoRI fragment, 3.8 kb, was cloned into lambda phage vector, and the deleted region of 10 kb including exons 2 and 3 was identified. The nucleotide sequence around the deletion joint was determined. The sequence of the eight nucleotides in the deletion-joint region of the mutant gene was identical to the corresponding sequences of both introns 1 and 3 of the normal gene. The deletion seemed to occur by an unequal recombination between the Alu-like sequences in the same direction in introns 1 and 3.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Southern
  • DNA / chemistry
  • DNA / genetics
  • Exons*
  • Female
  • Gene Deletion*
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Receptors, LDL / chemistry
  • Receptors, LDL / genetics*
  • Recombination, Genetic
  • Repetitive Sequences, Nucleic Acid*
  • Restriction Mapping

Substances

  • Receptors, LDL
  • DNA