The Trp23-Stop and Trp66-Gly mutations in the LDL receptor gene: common causes of familial hypercholesterolemia in Denmark

Atherosclerosis. 1996 Feb;120(1-2):57-65. doi: 10.1016/0021-9150(95)05680-7.

Abstract

Mutations in the gene for the low density lipoprotein (LDL) receptor cause the autosomal dominant disease familial hypercholesterolemia (FH), the prevalence of which is about 0.2% in most populations. By PCR-SSCP analysis and direct sequencing, we identified the receptor-negative Trp23-Stop LDL receptor mutation (FH Cincinnati-5) in 10 of 63 FH probands and the receptor-defective Trp66-Gly LDL receptor mutation (FH French Canadian-4) in another 10 of the 63 FH probands. These two mutations thus account for 30% of diagnosed FH families in Denmark. Comparison of the mean lipid concentrations (unadjusted and adjusted for age), including serum total cholesterol and LDL-cholesterol, showed no significant differences between the two groups of FH heterozygote probands (cholesterol: 10.7 mmol/l vs. 10.7 mmol/l) and between the probands and 16 and 22 non-proband family members with the Trp23-stop (cholesterol: 10.1 mmol/l) ad Trp66-Gly (cholesterol: 10.7 mmol/l) mutations, respectively.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Canada / epidemiology
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Codon / genetics
  • DNA Mutational Analysis
  • Denmark / epidemiology
  • Female
  • France / ethnology
  • Gene Frequency
  • Genes
  • Haplotypes / genetics
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / epidemiology
  • Hyperlipoproteinemia Type II / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Prevalence
  • Receptors, LDL / genetics*
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Codon
  • Receptors, LDL
  • Triglycerides
  • Cholesterol