Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

low density lipoprotein receptor

The lipoprotein receptor encoded by this gene allows liver cells to eliminate LDL particles from the blood. Mutations result in impaired function, which becomes noticable by elevated LDL cholesterol levels, cholesterol accumulation in the body, and accelerated arteriosclerosis.

Epidemiology

The prevalance of the homozygous form is 1:1.000.000. The allel frequency is 1:500.

Gene Structure

The gene of the low density lipoprotein receptor (LDLR) is about 45kb in size. I consists of 19 exons. Locus is on chromosome 19 (19p13.2). Structure and function of the protein domains are well known and explained here: www.nephrogene.de.

Phenotype

Biochemically we find a hyperlipimia of type IIa according to Fredrickson. But often a mutation of this gene is accompanied by other metabolic disturbancies and therefore Triglycerides may be elavated too. The typical clinical picture are xanthomas. You can find some examples following this link: www.nephrogene.de/.

Pathology

The task of this receptor is reabsorption of LDL particles from the blood stream into the hepatocytes. Apolipoprotein B is the corresponding ligand on LDL. If this reabsorption is disturbed the cholesterol rich LDL particles remain in the blood stream for a long time and they get oxidated and reabsorbed by scavanger receptors in some other cells including the endothelial cell. This initiates the process leading to artherosclerosis.

Test Strategy

Patients with hypercholesterolemia, when lipidapheresis is considered in therapy.

Interpretation

Mutations in have a great importance for the development of coronary heart disease.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Autosomal dominant hypercholesterolemia 1
LDLR
Arteriosclerosis
APOB
APOE
HABP2
LDLR
LPA
MTHFR
PON1
SLC3A1
Combined familial hyperlipidemia with dysfunctional LDL clearance
ATF6
LDLR
PCSK9

References:

1.

Varret M et al. (1997) Software and database for the analysis of mutations in the human LDL receptor gene.

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2.

Schuster H et al. (1998) DNA diagnosis of familial hypercholesterolemia.

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3.

Tybjaerg-Hansen A et al. (1998) Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease.

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Update: Sept. 26, 2018