Diagnosis of Familial Hypercholesterolaemia Using DNA Probes for the Low-Density Lipoprotein (LDL) Receptor Gene

1988 ◽  
Vol 25 (2) ◽  
pp. 142-149 ◽  
Author(s):  
A E Armston ◽  
S A Iversen ◽  
J F Burke
Keyword(s):  
Heart Disease ◽  
Familial Hypercholesterolaemia ◽  
Recombinant Dna ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Recombinant Dna Technology ◽  
Cholesterol Levels ◽  
Dna Technology

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.

scholarly journals Cholesterol Levels in Genetically Determined Familial Hypercholesterolaemia in Russian Karelia

Cholesterol ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
V. A. Korneva ◽  
T. Yu. Kuznetsova ◽  
T. Yu. Bogoslovskaya ◽  
D. S. Polyakov ◽  
V. B. Vasilyev ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Familial Hypercholesterolaemia ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Gene Mutations ◽  
Density Lipoprotein ◽  
Single Strand Conformation Polymorphism ◽  
Polymorphism Analysis ◽  
Cholesterol Levels

Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable.

Recombinant DNA technology and low-density lipoprotein receptor defects

1987 ◽  
Vol 15 (2) ◽  
pp. 202-203 ◽  
Author(s):  
JOHN DAVISON ◽  
BERHARD HORSTHEMKE ◽  
ALISON DUNNING ◽  
ROHAN TAYLOR ◽  
STEVE HUMPHRIES
Keyword(s):  
Recombinant Dna ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Recombinant Dna Technology ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Dna Technology

Identification of a deletion in the low density lipoprotein (LDL) receptor gene in a patient with familial hypercholesterolaemia

1985 ◽  
Vol 71 (1) ◽  
pp. 75-78 ◽  
Author(s):  
B. Horsthemke ◽  
Anna M. Kessling ◽  
Mary Seed ◽  
V. Wynn ◽  
R. Williamson ◽  
...  
Keyword(s):  
Familial Hypercholesterolaemia ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density

scholarly journals Review of the scientific evolution of gene therapy for the treatment of homozygous familial hypercholesterolaemia: past, present and future perspectives

2019 ◽  
Vol 56 (11) ◽  
pp. 711-717 ◽  
Author(s):  
Ricardo Rodriguez-Calvo ◽  
Luis Masana
Keyword(s):  
Gene Therapy ◽  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Cholesterol Levels ◽  
Current Therapies ◽  
Short Palindromic Repeat

Familial hypercholesterolaemia (FH) is a devastating genetic disease that leads to extremely high cholesterol levels and severe cardiovascular disease, mainly caused by mutations in any of the main genes involved in low-density lipoprotein cholesterol (LDL-C) uptake. Among these genes, mutations in the LDL receptor (LDLR) are responsible for 80%–90% of the FH cases. The severe homozygous variety (HoFH) is not successfully treated with standard cholesterol-lowering therapies, and more aggressive strategies must be considered to mitigate the effects of this disease, such as weekly/biweekly LDL apheresis. However, development of new therapeutic approaches is needed to cure HoFH. Because HoFH is mainly due to mutations in the LDLR, this disease has been proposed as an ideal candidate for gene therapy. Several preclinical studies have proposed that the transference of functional copies of the LDLR gene reduces circulating LDL-C levels in several models of HoFH, which has led to the first clinical trials in humans. Additionally, the recent development of clustered regularly interspaced short palindromic repeat/CRISPR-associated 9 technology for genome editing has opened the door to therapies aimed at directly correcting the specific mutation in the endogenous LDLR gene. In this article, we review the genetic basis of the FH disease, paying special attention to the severe HoFH as well as the challenges in its diagnosis and clinical management. Additionally, we discuss the current therapies for this disease and the new emerging advances in gene therapy to target a definitive cure for this disease.

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