BIOMAT Database Logo BIOMAT Database Logo

Diagnosis of familial hypercholesterolaemia using DNA probes for the low-density lipoprotein (LDL) receptor gene. 1988

A E Armston, and S A Iversen, and J F Burke
Department of Chemical Pathology, Royal Sussex County Hospital, Brighton, UK.

Familial hypercholesterolaemia (FH) is one of the most commonly inherited diseases. It is characterised by an abnormal LDL receptor resulting in a selective elevation of serum LDL and cholesterol levels. The correlation between FH and premature heart disease means that these patients contribute significantly to the number of individuals presenting with coronary heart disease. In the work described here cDNA probes to LDL-receptor were used to assess the usefulness of recombinant DNA technology to diagnose familial hypercholesterolaemia. A 3' probe to the LDL-receptor which detects a restriction fragment length polymorphism (RFLP) in linkage disequilibrium with normal and mutant LDL-receptor genes, was found to be potentially informative in 20% of the families studied. In addition a 5' probe to the LDL-receptor may be capable of directly detecting mutations in some 6% of families. We suggest that until further work has established other RFLP's or oligonucleotide probes are synthesised to directly detect mutant LDL-receptor genes, recombinant DNA technology is only of limited value for diagnosing familial hypercholesterolaemia.

UI MeSH Term Description Entries
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004274 DNA, Recombinant Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected. Genes, Spliced,Recombinant DNA,Spliced Gene,Recombinant DNA Research,Recombination Joint,DNA Research, Recombinant,Gene, Spliced,Joint, Recombination,Research, Recombinant DNA,Spliced Genes
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006938 Hyperlipoproteinemia Type II A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins). Hyperbetalipoproteinemia,Hypercholesterolemia, Essential,Hypercholesterolemia, Familial,Apolipoprotein B-100, Familial Defective,Apolipoprotein B-100, Familial Ligand-Defective,Familial Combined Hyperlipoproteinemia,Hyper-Low Density Lipoproteinemia,Hyper-Low-Density-Lipoproteinemia,Hyper-beta-Lipoproteinemia,Hypercholesterolemia, Autosomal Dominant,Hypercholesterolemia, Autosomal Dominant, Type B,Hypercholesterolemic Xanthomatosis, Familial,Hyperlipoproteinemia Type 2,Hyperlipoproteinemia Type IIa,Hyperlipoproteinemia Type IIb,Hyperlipoproteinemia, Type II,Hyperlipoproteinemia, Type IIa,LDL Receptor Disorder,Apolipoprotein B 100, Familial Defective,Apolipoprotein B 100, Familial Ligand Defective,Autosomal Dominant Hypercholesterolemia,Autosomal Dominant Hypercholesterolemias,Combined Hyperlipoproteinemia, Familial,Combined Hyperlipoproteinemias, Familial,Density Lipoproteinemia, Hyper-Low,Density Lipoproteinemias, Hyper-Low,Disorder, LDL Receptor,Disorders, LDL Receptor,Dominant Hypercholesterolemia, Autosomal,Dominant Hypercholesterolemias, Autosomal,Essential Hypercholesterolemia,Essential Hypercholesterolemias,Familial Combined Hyperlipoproteinemias,Familial Hypercholesterolemia,Familial Hypercholesterolemias,Familial Hypercholesterolemic Xanthomatoses,Familial Hypercholesterolemic Xanthomatosis,Hyper Low Density Lipoproteinemia,Hyper beta Lipoproteinemia,Hyper-Low Density Lipoproteinemias,Hyper-Low-Density-Lipoproteinemias,Hyper-beta-Lipoproteinemias,Hyperbetalipoproteinemias,Hypercholesterolemias, Autosomal Dominant,Hypercholesterolemias, Essential,Hypercholesterolemias, Familial,Hypercholesterolemic Xanthomatoses, Familial,Hyperlipoproteinemia Type 2s,Hyperlipoproteinemia Type IIas,Hyperlipoproteinemia Type IIbs,Hyperlipoproteinemia Type IIs,Hyperlipoproteinemia, Familial Combined,Hyperlipoproteinemias, Familial Combined,Hyperlipoproteinemias, Type II,Hyperlipoproteinemias, Type IIa,LDL Receptor Disorders,Lipoproteinemia, Hyper-Low Density,Lipoproteinemias, Hyper-Low Density,Receptor Disorder, LDL,Receptor Disorders, LDL,Type 2, Hyperlipoproteinemia,Type II Hyperlipoproteinemia,Type II Hyperlipoproteinemias,Type IIa Hyperlipoproteinemia,Type IIa Hyperlipoproteinemias,Xanthomatoses, Familial Hypercholesterolemic,Xanthomatosis, Familial Hypercholesterolemic

Related Publications

A E Armston, and S A Iversen, and J F Burke
Familial hypercholesterolaemia: mutations in the gene for the low-density-lipoprotein receptor.
May 1995, Molecular medicine today,
A E Armston, and S A Iversen, and J F Burke
Identification of a deletion in the low density lipoprotein (LDL) receptor gene in a patient with familial hypercholesterolaemia.
January 1985, Human genetics,
A E Armston, and S A Iversen, and J F Burke
DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia.
June 1991, Clinical genetics,
A E Armston, and S A Iversen, and J F Burke
Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia.
December 2000, Journal of inherited metabolic disease,
A E Armston, and S A Iversen, and J F Burke
Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.
December 1987, Journal of medical genetics,
A E Armston, and S A Iversen, and J F Burke
DNA deletions and DNA polymorphisms of the low density lipoprotein (LDL) receptor gene--their use in diagnosis.
January 1986, Verhandlungen der Deutschen Gesellschaft fur Innere Medizin,
A E Armston, and S A Iversen, and J F Burke
The identification of two low-density lipoprotein receptor gene mutations in South African familial hypercholesterolaemia.
October 1989, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde,
A E Armston, and S A Iversen, and J F Burke
Low density lipoprotein--receptor (LDL-R) gene mutations among Filipinos with familial hypercholesterolemia.
January 2005, Journal of atherosclerosis and thrombosis,
A E Armston, and S A Iversen, and J F Burke
Deletions of the low density lipoprotein receptor gene underlying familial hypercholesterolaemia: screening by polymerase chain reaction using pooled DNA and blood samples.
February 1997, Molecular and cellular probes,
A E Armston, and S A Iversen, and J F Burke
Molecular genetics of familial hypercholesterolaemia: common and rare mutations of the low density lipoprotein receptor gene.
October 1992, Annals of medicine,
Copied contents to your clipboard!