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.
The prevalance of the homozygous form is 1:1.000.000. The allel frequency is 1:500.
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.
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/.
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.
Patients with hypercholesterolemia, when lipidapheresis is considered in therapy.
Mutations in have a great importance for the development of coronary heart disease.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 20 days | |
Specimen type | genomic DNA |
Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
Turnaround | 20 days | |
Specimen type | genomic DNA |
1. |
Varret M et al. (1997) Software and database for the analysis of mutations in the human LDL receptor gene. |
2. |
None (1998) DNA diagnosis of familial hypercholesterolemia. |
3. |
Tybjaerg-Hansen A et al. (1998) Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease. |
4. |
Orphanet article Orphanet ID 123021 |
5. |
NCBI article NCBI 3949 |
6. |
OMIM.ORG article Omim 606945 |
7. |
Wikipedia article Wikipedia EN (LDL_receptor) |