Test ID: APO1K
Apolipoprotein A-I (APOA1) Gene, Known Mutation
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Testing of individuals at risk for apolipoprotein A-I (APOA1) gene-associated amyloidosis when a mutation has been identified in an affected family member
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Documentation of the specific familial mutation(s) must be provided with the specimen in order to perform this test.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
APOAI
Apolipoprotein A-I
Amyloidosis
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test can only be performed if a mutation has previously been identified in a family member of this individual.
Specimen must arrive within 96 hours of draw.
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.
Forms:
1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet (Supply T521) in Special Instructions
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Plasma or serum |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Frozen | ||
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 50-93 and 170-178.
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.
It is important to note that this assay does not detect mutations associated with non-APOA1 forms of familial amyloidosis. Therefore, it is important to first test an affected family member to determine if APOA1 is involved and to document a specific mutation in the family before testing at risk individuals.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order APO1S/60723 Apolipoprotein A-I (APOA1) Gene, Full Gene Analysis.
Analysis is performed for the familial mutation(s) provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with familial amyloidosis
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Predictive testing of an asymptomatic child is not recommended.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions for testing patients who have received a bone marrow transplant.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. 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
2. Benson MD: Ostertage revisited: The inherited systemic amyloidoses without neuropathy. Amyloid 2005:12(2):75-80
3. von Eckardstein A: Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 2006;186:231-239
4. 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
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing is utilized to test for the presence of a mutation(s) in the apolipoprotein A-I (APOA1) gene that was previously identified in an affected family member.(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Wednesday 10 am
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479-Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 33393 | Specimen | N/A |
| 33394 | Specimen ID | N/A |
| 33395 | Source | N/A |
| 33396 | Order Date | N/A |
| 33397 | Reason For Referral | N/A |
| 33398 | Method | N/A |
| 33399 | Result | N/A |
| 33400 | Interpretation | N/A |
| 33401 | Amendment | N/A |
| 33402 | Reviewed By | N/A |
| 33403 | Release Date | N/A |
External
link
PDF
document
Excel
document
Word
document