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THE AMBRY TEST :
Alpha-1-Antitrypsin Deficiency
Alpha-1-Antitrypsin (AAT) Deficiency is a common genetic disorder predisposing to respiratory and hepatic disease.
AAT Deficiency has codominant inheritance, with each allele contributing individually to the patient’s phenotype.
Alleles are named with a protease inhibitor or “PI” type. Patients with the most common severe form of the disease (homozygous Z alleles, or PI*Z/PI*Z) are at increased risk of neonatal cholestasis; juvenile or adult cirrhosis, some- times requiring liver transplant; and chronic obstructive pulmonary disease including early-onset emphysema. Less frequent complications include hepatocellular carcinoma, panniculitis, and vasculitis. The less severe S allele causes reduced serum levels of AAT. Null alleles produce little or no protein. Either the S or a null allele may cause symp- toms when present in combination with another severe deficiency allele.
While not all patients with AAT Deficiency will have clinically significant symptoms, the condition is considered wide- ly under-recognized.1,2 Over 300,000 people in the U.S. and Canada are estimated to have PI SZ or PI ZZ pheno- types.3 In these countries, approximately 1/44 people are carriers of the Z allele and 1/17 carry the S allele.3 AAT Deficiency affects all racial subgroups.3 More than 100 variants in the AAT gene have been described, with over one third of those known to cause abnormal protein expression.2 Rare genetic variants are collectively not so rare, causing approximately 5% of deficiency cases.1 The American Thoracic Society and the European Respiratory Society have published guidelines for testing in symp- tomatic individuals and those at increased risk due to family history or environmental exposures.2 Routine serum pro- tein measurement and phenotyping are adequate in most cases.
The Ambry Test is a valuable adjunct to those biochemical tests and is appropriate for: ■ resolving discrepancies and ambiguities between clinical presentation, protein measurement, and/or phenotyping
■ carrier testing for relatives of patients with known mutations
Please see our Gene Report: The Role of Full Gene Sequence Analysis in the Diagnosis of Alpha-1-Antitrypsin Deficiency for a more detailed discussion of situations that can complicate or prevent a correct biochemical diagno- sis. The Ambry Test, as a complete molecular analysis, can resolve the patient’s diagnosis at the DNA level.
This Ambry Test is a full gene analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 2 through 5 of the SERPINA 1 gene, plus at least 20 base pairs into the the 5’ and3’ ends of all introns. Specific mutation analysis for known family mutations in SERPINA 1 is also available.
The Ambry Test: Alpha-1-Antritryspin Deficiency clinical mutation detection rate is approximately 99%.
Specific mutation analysis . 10 – 14 days The Ambry Test®: Alpha-1-Antitrypsin Deficiency BLOOD: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD
yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
SALIVA: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
PRENATAL: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
Full gene analysis or specific mutation analysis . 83891, 83894, 83898, 83904, 83909, 83912 1World Health Organization. Bulletin of the WHO. 1997;75:397-415.
2American Thoracic Society and European Respiratory Society. Am J Respir Crit Care Med. 2003;168:818-900.
3deSerres FJ. Chest. 2002;122:1818-1829.
Ambry Genetics | 100 Columbia #200, Aliso Viejo, CA 92656 | www.ambrygen.com | toll-free 866-262-7943 | ph 949-900-5500 | fax 949-900-5501
2008 Ambry Genetics P0408-09-012-MKG-00

Source: http://dev4.group22.com/clinical_diagnostic_and_carrier_testing/PDFforms/1.2.1.2%20AAT%20Test.pdf