Rapid screening for specific mutations in patients with a clinical diagnosis of familial hypercholesterolaemia

Atherosclerosis. 1991 Aug;89(2-3):137-41. doi: 10.1016/0021-9150(91)90053-6.


We describe a rapid screening procedure to identify known DNA sequence changes in individuals diagnosed as having heterozygous familial hypercholesterolaemia (FH). The screening is made possible by combining a rapid DNA extraction protocol and small scale polymerase chain reaction DNA amplification, followed by oligonucleotide melting or restriction enzyme digestion. We have screened for two different mutations; firstly a mutation in the apolipoprotein B (apo B) gene that results in the substitution of glutamine (Gln) for arginine (Arg) at amino acid residue 3500 (apo B3500 mutation). Apo B is the principal component of the protein moiety of low density lipoprotein (LDL) and the mutation reduces the affinity for the LDL receptor (LDL-R). Secondly we have screened for a point mutation in the LDL-R gene itself that creates a new Pst I restriction enzyme site. This mutation in the LDL-R gene (LDL-R664 mutation) results in the substitution of leucine (Leu) for proline (Pro) at amino acid 664 and is known to slow processing of the LDL-R precursor to the mature form and to reduce the affinity of the receptor on the cell surface for LDL. In 77 unrelated patients with a clinical diagnosis of FH two out of 77 (2.6%) were positive for the apo B3500 mutation. Three (3.9%) were positive for the LDL-R664 mutation. Thus these two mutations might account for 5-6% of patients in the U.K. with a clinical diagnosis of FH (5000-6000 people).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins B / genetics
  • Female
  • Genetic Testing / methods*
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / diagnosis*
  • Hyperlipoproteinemia Type II / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Oligonucleotide Probes
  • Polymerase Chain Reaction
  • Receptors, LDL / genetics


  • Apolipoproteins B
  • Oligonucleotide Probes
  • Receptors, LDL