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Test ID: APO1Z Apolipoprotein A-I (APOA1) Gene, Full Gene Analysis

Useful For

Diagnosis of individuals suspected of having apolipoprotein A-I (APOA1) gene-associated familial amyloidosis

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

APOA1 Gene, Full Gene Analysis

Specimen Type

Varies


Specimen Required


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: Specimen preferred to arrive within 96 hours of draw.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
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) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Test 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 U.S. 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 In Process

 

Result ID Test Result Name Result LOINC Value
52988 Result Summary 50397-9
52989 Result In Process
52990 Interpretation 69047-9
52991 Additional Information 48767-8
52992 Specimen 31208-2
52993 Source 31208-2
52994 Released By No LOINC Needed

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 (T576) is available in Special Instructions.

2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular