Test ID: APO1Z Apolipoprotein A-I (APOA1) Gene, Full Gene Analysis, Varies
Useful For
Diagnosis of individuals suspected of having apolipoprotein A-I (APOA1) gene-associated familial amyloidosis
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
Reporting Name
APOA1 Gene, Full Gene AnalysisSpecimen Type
VariesShipping Instructions
Specimen preferred to arrive within 96 hours of draw.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Frozen | |||
Refrigerated |
Clinical Information
The systemic amyloidoses are a number of disorders of varying etiology characterized by extracellular protein deposition. The most common form is an acquired amyloidosis secondary to multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) in which the amyloid is composed of immunoglobulin light chains. In addition to light chain amyloidosis, there are a number of acquired amyloidoses caused by the misfolding and precipitation of a wide variety of proteins. There are also hereditary forms of amyloidosis.
The hereditary amyloidoses comprise a group of autosomal dominant, late-onset diseases that show variable penetrance. A number of genes have been associated with hereditary forms of amyloidosis including those that encode transthyretin, apolipoprotein A-I, apolipoprotein A-II, fibrinogen alpha chain, gelsolin, cystatin C, and lysozyme. Apolipoprotein A-I, apolipoprotein A-II, lysozyme, and fibrinogen alpha-chain amyloidosis present as non-neuropathic systemic amyloidosis, with renal dysfunction being the most prevalent manifestation. Apolipoprotein A-I amyloidosis is also associated with additional organ system involvement, including clinical manifestations in the liver, heart, skin, and larynx. In addition, the G26R APOA1 mutation has been associated with a neuropathic presentation.
To date, at least 16 amyloidogenic mutations have been identified within the APOA1 gene. The majority of these are missense mutations, although deletion/insertion mutations have also been described. There is some evidence of genotype-phenotype correlations. Mutations that occur near the amino terminal portion of the protein are more often associated with hepatic and renal amyloidosis, while mutations occurring near the carboxyl terminal portion of the gene are more often associated with cardiac, cutaneous, and laryngeal amyloidosis. The majority of mutations reported to date occur at 1 of 2 hot spots spanning amino acid residues 50 through 93 and 170 through 178.
Mutations in the APOA1 gene have also been linked to familial hypoalphalipoproteinemia. Patients carrying 1 APOA1 mutation typically demonstrate reduced levels of high-density lipoprotein (HDL) cholesterol, which is associated with increased risk for coronary artery disease. Comparatively, the presence of 2 APOA1 mutations generally results in complete absence of HDL cholesterol and may include additional clinical features such as xanthomas or corneal opacities.
Due to the clinical overlap between the acquired and hereditary forms, it is imperative to determine the specific type of amyloidosis in order to provide an accurate prognosis and consider appropriate therapeutic interventions. Tissue-based, laser capture tandem mass spectrometry might serve as a useful test preceding gene sequencing to better characterize the etiology of the amyloidosis, particularly in cases that are not clear clinically.
Reference Values
An interpretive report will be provided.
Interpretation
All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424
2. Eriksson M, Schonland S, Yumlu S, et al: Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene. J Mol Diagn 2009;11(3):257-262
3. Benson MD: Ostertage revisited: The inherited systemic amyloidoses without neuropathy. Amyloid 2005:12(2):75-80
4. von Eckardstein A: Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 2006;186:231-239
5. Shiller SM, Dogan A, Highsmith WE: Laboratory methods for the diagnosis of hereditary amyloidoses. In Amyloidosis-Mechanisms and Prospects for Therapy. Edited by S Sarantseva. InTech 2011, pp 101-120
Day(s) Performed
Varies
Report Available
14 to 20 daysTest Classification
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479-Unlisted molecular pathology procedure
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
APO1Z | APOA1 Gene, Full Gene Analysis | 93420-8 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
52988 | Result Summary | 50397-9 |
52989 | Result | 82939-0 |
52990 | Interpretation | 69047-9 |
52991 | Additional Information | 48767-8 |
52992 | Specimen | 31208-2 |
52993 | Source | 31208-2 |
52994 | Released By | 18771-6 |
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions
3. If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.
mml-inherited-molecular