Test ID: APO2K
Apolipoprotein A-II (APOA2) Gene, Known Mutation

Testing individuals at risk for apolipoprotein A-II-associated amyloidosis when a mutation has been identified in an affected family member

Documentation of the specific familial mutation(s) must be provided with the specimen in order to perform this test.

• Molecular Genetics-Biochemical Disorders Patient Information Sheet
• Informed Consent for Genetic Testing

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

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. Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet (Supply T521) in Special Instructions

2. 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.

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-II amyloidosis typically presents as a very slowly progressive disease. Age of onset is highly variable, ranging from adolescence to the fifth decade. To date all mutations that have been identified within the APOA2 gene occur within the stop codon and result in a 21-residue C-terminal extension of the apolipoprotein A-II protein.

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-APOA2 forms of familial amyloidosis. Therefore, it is important to first test an affected family member to determine if APOA2 is involved and to document a specific mutation in the family before testing at risk individuals.

An interpretive report will be provided.

An interpretive report will be provided.

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 APO2S/60725 Apolipoprotein A-II (APOA2) 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 for instructions for testing patients who have received a bone marrow transplant.

1. Benson MD. Ostertage revisited: The inherited systemic amyloidoses without neuropathy. Amyloid 2005;12(2):75-80

2. Benson MD, Liepnieks JJ, Yazaki M, et al: A new human hereditary amyloidosis: The result of a stop-codon mutation in the Apolipoprotein AII gene. Genomics 2001;72:272-277

3. Yazaki M, Liepnieks JJ, Yamashita T, et al: Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene. Kidney Int 2001;60:1658-1665

4. Yazaki M, Liepnieks JJ, Barats MS, et al: Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg. Kidney Int 2003;64:11-16

DNA sequence analysis is used to determine the presence or absence of the mutation previously identified in a family member of the patient.(Unpublished Mayo method)

Wednesday 10 am

81479-Unlisted molecular pathology procedure