Low density lipoprotein receptor mutations in a selected population of individuals with moderate hypercholesterolemia

Atherosclerosis. 1998 Jan;136(1):187-94. doi: 10.1016/s0021-9150(97)00210-4.


To evaluate mutations in the low density lipoprotein receptor (LDL-R) gene in moderate primary hypercholesterolemia, a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing, was used to screen the LDL-R gene in a selected population of 82 unrelated individuals with moderate elevation of plasma LDL-C [mean 4.55 +/- 0.55 mmol/l (176.4 +/- 21.6 mg/dl)]. Four subjects (5%) were found to be heterozygotes for missense mutations in the LDL-R gene. These mutations were located in four different exons (exons 6, 7, 15 and 17) and all alters highly conserved residues of LDL-R protein. None of these mutations were detected in 79 normocholesterolemic individuals. The mutation in exon 15 (T705I) was previously reported in a compound heterozygote for familial hypercholesterolemia (FH). In the proband carrying the mutation in exon 17 (R793Q), an in vivo LDL turnover study was performed and it demonstrated a reduction of LDL catabolism. These findings demonstrate that mutations in the LDL-R may occur in primary moderate hypercholesterolemia. They also extend the concept that some FH patients may present with a mild phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Exons
  • Humans
  • Hypercholesterolemia / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptors, LDL / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA


  • Receptors, LDL