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Test ID: SERPZ SERPINA1 Gene, Full Gene Analysis


Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



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.


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 and Forms.

Useful For

Identification of causative mutations when a deficient serum level of alpha-1-antitrypsin is not explained by routine testing, such as proteotyping, genotyping, or isoelectric focusing phenotyping.

 

Determining the specific allelic variant (full gene analysis) for prognosis and genetic counseling

Testing Algorithm

See Alpha-1 Antitrypsin-A Comprehensive Testing Algorithm in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing

Reporting Name

SERPINA1 Gene, Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Refrigerated (preferred)
  Ambient 
  Frozen 

Clinical Information

Alpha-1-antitrypsin (A1A) is a protein that inhibits the enzyme neutrophil elastase. It is predominantly synthesized in the liver and secreted into the bloodstream. The inhibition function is especially important in the lungs because it protects against excess tissue degradation. Tissue degradation due to A1A deficiency is associated with an increased risk for early onset panlobular emphysema, which initially affects the lung bases (as opposed to smoking-related emphysema, which presents with upper lung field emphysema). Patients may become symptomatic in their 30s and 40s. The most frequent symptoms reported in a National Institute of Health study of 1,129 patients with severe deficiency (mean age 46 years) included cough (42%), wheezing (65%), and dyspnea with exertion (84%). Many patients were misdiagnosed as having asthma. It is estimated that approximately one-sixth of all lung transplants are for A1A deficiency.

 

Liver disease can also occur, particularly in children; it occurs much less commonly than emphysema in adults.

 

A1A deficiency is a relatively common disorder in Northern European Caucasians. The diagnosis of A1A deficiency is initially made by quantitation of protein levels in serum followed by phenotyping-determination of specific allelic variants by isoelectric focusing (IEF), genotyping-DNA based detection of specific mutations, or proteotyping-using liquid chromatography-tandem mass spectrometry (LC-MS/MS). While there are many different alleles in this gene, only 3 are common. The 3 major alleles include: M (full functioning, normal allele), S (associated with reduced levels of protein), and Z (disease-causing mutation associated with liver disease and premature emphysema). The S and Z alleles account for the majority of the abnormal alleles detected in affected patients. As a codominant disorder, both alleles are expressed. An individual of SZ or S- null genotype may have a small increased risk for emphysema (but not liver disease) due to slightly reduced protein levels. On the other hand, an individual with the ZZ genotype is at greater risk for early onset liver disease and premature emphysema.

 

Smoking appears to hasten development of emphysema by 10 to 15 years. These individuals should be monitored closely for lung and liver function.

 

Historically, IEF phenotyping has been the primary method for characterizing variants, though in some cases the interpretation is difficult and prone to error. Serum quantitation is helpful in establishing a diagnosis but can be influenced by other factors. IEF phenotyping, LC-MS/MS proteotyping, and DNA-based genotyping are routinely used to test for deficiency alleles, but can miss disease alleles other than the S and Z alleles. In patients suspected to have alpha-1 antitrypsin deficiency based on clinical findings or serum alpha-1-antitrypsin (AAT) levels, who do not have evidence of the SZ or ZZ genotype by routine methods, this gene analysis assay may provide useful information. Full sequencing of the SERPINA1 coding region is performed for the detection of rare non-S or non-Z disease mutations.

 

See Alpha-1-Antitrypsin-A Comprehensive Testing Algorithm in Special Instructions.

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. Stoller JK, Aboussouan LS: Alpha-1-antitrypsin deficiency. Lancet 2005;365:2225-2236

3. McElvaney NG, Stoller JK, Buist AS, et al: Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute Registry of alpha 1-antitrypsin deficiency. Alpha 1-Antitrypsin Deficiency Registry Study Group. Chest 1997;111:394-403

4. Snyder MR, Katzmann JA, Butz ML, et al: Diagnosis of alpha-1-antitrypsin deficiency: an algorithm of quantification, genotyping, and phenotyping. Clin Chem 2006;52:2236-2242

5. Graham RP, Dina MA, Howe SC, et al: SERPINA1 full-gene sequencing identifies rare mutations not detected in targeted mutation analysis. J Mol Diag 2015;17:689-694

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

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SERPZ SERPINA1 Gene, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
113178 Result Summary 50397-9
113179 Result In Process
113180 Interpretation In Process
113181 Additional Information In Process
113182 Specimen 31208-2
113183 Source 31208-2
113184 Released By In Process
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular