PMID: 9547893Apr 21, 1998Paper

Simplified detection of a mutation causing familial hypercholesterolaemia throughout Britain: evidence for an origin in a common distant ancestor

Annals of Clinical Biochemistry
P R WenhamS W Walker

Abstract

Familial hypercholesterolaemia (FH) is an inherited autosomal codominant disorder caused by many different mutations in the low-density lipoprotein receptor (LDLR) gene. The one described most frequently in patients with FH from England, arises from a G-->A transition at the first nucleotide of codon 80, resulting in the substitution of lysine for glutamic acid at residue 80 of the mature protein, FH E80K. We describe a simple method to detect this mutation in genomic DNA using the polymerase chain reaction (PCR). A 69 base pair (bp) fragment of exon 3 of the LDLR gene is amplified using a mutagenic upstream PCR primer. This substitutes a T for an A residue in the amplified product, 2 bp upstream from the mutant site, generating a restriction site for the endonuclease Taq I, in normal, but not in mutant DNA. Following digestion of amplified DNA with Taq I, normal but not mutant DNA is cut into two fragments of 29 and 40 bp, which are readily identified by polyacrylamide gel electrophoresis. Using this method, 410 patients with clinically diagnosed FH, attending lipid clinics in Edinburgh (72), Newport (158), Walsall (30) and Southampton (150), were screened for the mutation. Five individuals tested positive as heterozygotes, on...Continue Reading

References

Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
Aug 11, 1991·Nucleic Acids Research·A K Soutar
Apr 1, 1990·The Journal of Clinical Investigation·E LeitersdorfH H Hobbs
Jul 25, 1988·Nucleic Acids Research·E Leitersdorf, H H Hobbs
Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
May 1, 1995·Human Molecular Genetics·A C PetersonN B Freimer
Jul 1, 1993·Human Molecular Genetics·W J WallB H Parkin

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Citations

May 27, 2011·Journal of Clinical Lipidology·Paul N HopkinsUNKNOWN National Lipid Association Expert Panel on Familial Hypercholesterolemia

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