Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia

Hum Mutat. 1997;10(2):116-27. doi: 10.1002/(SICI)1098-1004(1997)10:2<116::AID-HUMU4>3.0.CO;2-I.


Familial hypercholesterolemia by usual definition reflects mutations of the LDL-receptor gene. Extensive molecular characterization of mutations ascertained mainly through homozygotes (the Dallas collection) has been presented by Hobbs et al. (Hum Mutat 1:445-446, 1992). This paper catalogues a spectrum of 134 mutations (27 novel mutations in 45 patients, 24 previously described mutations in 89 patients) ascertained through heterozygotes from the analysis of 791 patients with definite, probable, or possible FH, mainly from the UK, using high-throughput modifications of the single-strand conformation polymorphism technique. From a composite database of LDL receptor gene mutations complied from these two sets and from the literature, deductions are made about ascertainment bias, mutation rates, and molecular heterogeneity. Calculations suggest that there may be a large number of rare amino acid variants in the general population not causing classic FH. Approaches to, and feasibility of, molecular diagnostics are considered.

Publication types

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

MeSH terms

  • Genetic Variation
  • Heterozygote*
  • Humans
  • Hypercholesterolemia / genetics*
  • Mutation*
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single-Stranded Conformational*
  • Promoter Regions, Genetic
  • Receptors, LDL / genetics*
  • Sequence Analysis, DNA / methods


  • Receptors, LDL