DNA Deletions and DNA Polymorphisms of the Low Density Lipoprotein (LDL) Receptor Gene — Their Use in Diagnosis
We have used a cloned cDNA probe for the human LDL receptor gene to look for gross alterations in the LDL receptor gene in patients with Familial Hypercholesterolemia (FH). Among 60 UK patients analysed, we have identified 4 patients where FH appears to be caused by deletion of coding sequences either from the 3′ or from the central part of the gene. Presymptomatic diagnosis based on DNA analysis will thus be possible for these families. Presymptomatic diagnosis in the families of the other patients, relies on the use of indirect methods. The LDL receptor gene cDNA probe detects a common restriction fragment length polymorphism (RFLP) with the enzyme PvuII. The variable PvuII site appears to be within an intervening sequence in the 3’ part of the gene. The rare allele frequency of this polymorphism in both normolipidaemic individuals and patients with heterozygous FH is 0.23. Thirty percent of individuals are heterozygous for the polymorphism and their families are thus potentially informative for early diagnosis of FH based on genetic linkage analysis.
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- 3.Frederickson DS, Goldstein JL, Brown MS (1978) The familial hyperlipoproteinaemias. In: Stanbury JB, Wyngaarden JB and Frederickson DS (eds) The metabolic basis of inherited disease, McGraw-Hill, New York, pp, 604–655Google Scholar
- 6.Horsthemke B, Beisiegel U, Dunning A, Williamson R, Humphries S (in preparation) Non-homologous crossing-over between two alu-repetitive DNA sequences in the LDL receptor gene: A possible mechanism for a novel mutation in a patient with familial hypercholesterolaemiaGoogle Scholar
- 7.Horsthemke B, Dunning A, Humphries S (in preparation) Identification of deletions in the human low-density lipoprotein (LDL) receptorGoogle Scholar
- 14.Lipid Research Clinics Program (1984) The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 251:356–374Google Scholar