Mutation analysis reveals an insertional hotspot in exon 4 of the LDL receptor gene

Hum Genet. 1996 Oct;98(4):476-8. doi: 10.1007/s004390050242.


Mutation analysis of the low density lipoprotein receptor (LDLR) gene revealed a novel 8-bp duplication after nucleotide 681 in a Costa Rican patient with familial hypercholesterolaemia. The frameshift caused by this mutation results in a premature termination codon in the EGF precursor homology domain of the mature LDLR, whereby a truncated protein of the first 206 residues with an additional 39 abnormal residues would be created. The insertion overlaps with previously described duplications of 18 bp and 21 bp, thus revealing an insertional hotspot in exon 4 of the LDLR gene. We propose that the structural features of this region of the LDLR gene contribute significantly to genetic instability and the subsequent DNA duplication via an endogenous sequence-directed mechanism of mutagenesis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Codon
  • DNA Mutational Analysis
  • DNA Primers
  • DNA Transposable Elements*
  • Epidermal Growth Factor / genetics
  • Exons*
  • Female
  • Frameshift Mutation*
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Receptors, LDL / genetics*
  • Terminator Regions, Genetic
  • Triglycerides / blood


  • Cholesterol, HDL
  • Codon
  • DNA Primers
  • DNA Transposable Elements
  • Receptors, LDL
  • Triglycerides
  • Epidermal Growth Factor
  • Cholesterol