Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
Mutations that result in defective apolipoprotein B cause a rare but severe disease, abetalipoproteinemia. More common are mutations with impaired LDL receptor binding and elevated LDL cholesterol.
The prevalance of the homozygous form is 1:1.000.000. The allel frequency is 1:500.
Apolipoprotein B (ApoB) exists in two different versions called ApoB100 and ApoB48. In enterocytes a posttranscriptional modification of the mRNA takes place. As a result of this modification a stop codon is generated and translation is aborted when 48% of the protein is synthesized. There is no LDL receptor ligand in ApoB48.
Phenotypically there is no difference between mutations affecting ligand region in ApoB100 and LDL receptor mutations. Patients have a significant hypercholesterinemia. In lipidelectrophoresis we see a predomination of LDL particles According to Fredrickson this hyperlipemia is classified typ II. The chance for oxydation of these particles and by this way the risk for cardiovascular disease is high.
ApoB100 is secreted by hepatocytes together with VLDL. Enterocytes secrete ApoB48 in chylomikrones. Functioning ApoB100 can be reabsorbed by hepatocytes via LDL receptor. Chylomikrons containing ApoB48 hepatocytes by other mechanisms. Mutations in ApoB100 affecting the ligand lead to increase of cholesterol rich LDL particles. The effect is just the same as in LDL receptor mutations.
Apolipoprotein B mutations and LDL receptor mutation should be screened together.
| 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 | Target mutation analysis |
| Turnaround | 20 days | |
| Specimen type | genomic DNA |
| 1. |
Vrablík M et al. (2001) Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis. 
|
| 2. |
None (2003) Familial hypobetalipoproteinemia: a review.
|
| 3. |
Whitfield AJ et al. (2004) Lipid disorders and mutations in the APOB gene.
|
| 4. |
Schonfeld G et al. (2005) Familial hypobetalipoproteinemia: genetics and metabolism.
|
| 5. |
Parhofer KG et al. (2006) Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies.
|
| 6. |
Soria LF et al. (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.
|
| 7. |
Orphanet article Orphanet ID 121386
|
| 8. |
NCBI article NCBI 338
|
| 9. |
OMIM.ORG article Omim 107730
|
| 10. |
Wikipedia article Wikipedia EN (Apolipoprotein_B)
|
 |
Copyright © 2005-2025 by Center for Nephrology and Metabolic Disorders, Dr. Mato Nagel, MD Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Germany, Tel.: +49-3576-287922, Fax: +49-3576-287944 Sitemap | Webmail | Disclaimer | Privacy Issues | Website Credits |
