Confirm a diagnosis of familial defective Apo B-100 (FDB). Identify genetic cause for inherited hypercholesterolemia. Screen individuals with a family history of FDB to assess risk of coronary artery disease.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
R3500W Negative: This patient is negative for the R3500W (C9774T) mutation.
Characteristics: Familial defective APOB-100 (FDB) is a disorder which increases an individual's risk for coronary artery disease. FDB is caused by mutations in the APOB gene that prevents the APOB-LDL complex from binding to the LDL receptor.
Incidence: 1.5 percent of familial hypercholesterolemia is due to an APOB gene mutation. The most common mutation, Arg3500Gln, has a frequency of 1/500-1/700 in Caucasian populations of North America and Europe. The rare Arg3500Trp mutation originally described in the Scottish population has also been identified in FDB of Asian descent (approximately 2 percent of FDB patients).
Inheritance: Autosomal dominant
Penetrance: Heterozygous carriers of an APOB mutation have an increased risk for coronary artery disease, although with a reduced penetrance. 40 percent of males and 20 percent of females heterozygous for these mutations develop coronary artery disease. Homozygotes or compound heterozygotes for R3500Q/R3500W are at greater risk for disease.
Cause: Ligand-defective apolipoprotein B-100.
Methodology: Patient DNA is assayed for Arg3500Gln and Arg3500Trp mutations in the APOB gene by polymerase chain reaction (PCR) and fluorescence monitoring using hybridization probes.
Analytical Sensitivity & Specificity: Sensitivity and specificity for detection of this mutation are 99.9 percent.
Limitations: Mutations in other genes or other mutations in the APOB gene that may cause familial hypercholesterolemia or increased risk for coronary artery disease are not ruled out. Diagnostic errors can occur due to rare sequence variations.
This test is not recommended for nonsymptomatic patients under 18 years of age.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0055654||Apolipoprotein B Mutation Detection||73748-6|
|2001297||Apolipoprotein B Specimen||31208-2|
- APO B Cardiac Risk
- APOB-100 mutations
- Apolipoprotein B
- Apolipoprotein B-100