Clinical Chemistry
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 52: 2236-2242, 2006. First published October 19, 2006; 10.1373/clinchem.2006.072991
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
Right arrow All Versions of this Article:
clinchem.2006.072991v1
52/12/2236    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Thibodeau, S. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Snyder, M. R.
Right arrow Articles by Thibodeau, S. N.
Related Collections
Right arrow Evidence Based Laboratory Medicine and Test Utilization
(Clinical Chemistry. 2006;52:2236-2242.)
© 2006 American Association for Clinical Chemistry, Inc.

Evidence-Based Laboratory Medicine and Test Utilization

Diagnosis of {alpha}-1-Antitrypsin Deficiency: An Algorithm of Quantification, Genotyping, and Phenotyping

Melissa R. Snyder1, Jerry A. Katzmann1,2,a, Malinda L. Butz3, Ping Yang4, D. Brian Dawson3, Kevin C. Halling3, W. Edward Highsmith3 and Stephen N. Thibodeau3

1 Division of Clinical Biochemistry & Immunology, Department of Laboratory Medicine & Pathology, 2 Division of Hematology, Department of Internal Medicine, 3 Division of Laboratory Genetics, Department of Laboratory Medicine & Pathology, 4 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.

aAddress correspondence to this author at: Mayo Clinic, 200 First St SW, Rochester, MN 55905. Fax 507-266-4088; e-mail Katzmann.Jerry{at}mayo.edu.

Background: Laboratory testing in suspected {alpha}-1-antitrypsin (A1AT) deficiency involves analysis of A1AT concentrations and identification of specific alleles by genotyping or phenotyping. The purpose of this study was to define and evaluate a strategy that provides reliable laboratory evaluation of A1AT deficiency.

Methods: Samples from 512 individuals referred for A1AT phenotype analysis were analyzed by quantification, phenotype, and genotype. A1AT concentrations were measured by nephelometry. Phenotype analysis was performed by isoelectric focusing electrophoresis. The genotype assay detected the S and Z deficiency alleles by a melting curve analysis.

Results: Of the 512 samples analyzed, 2% of the phenotype and genotype results were discordant. Among these 10 discordant results, 7 were attributed to phenotyping errors. On the basis of these data we formulated an algorithm, according to which we analyzed samples by genotyping and quantification assays, with a reflex to phenotyping when the genotype and quantification results were not concordant. Retrospective analyses demonstrated that 4% of samples submitted for genotype and quantitative analysis were reflexed to phenotyping. Of the reflexed samples, phenotyping confirmed the genotype result in 85% of cases. In the remaining 15%, phenotyping provided further information, including identifying rare deficiency alleles and suggesting the presence of a null allele, and allowed for a more definitive interpretation of the genotype result.

Conclusions: The combination of genotyping and quantification, with a reflex to phenotyping, is the optimal strategy for the laboratory evaluation of A1AT deficiency.




The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
M. L. Snyder and C. R. Fantz
Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis
Clin. Chem., August 1, 2008; 54(8): 1395 - 1398.
[Full Text] [PDF]

Home page
 Clin. Chem.Home page
M. Dahl
Commentary
Clin. Chem., August 1, 2008; 54(8): 1398 - 1399.
[Full Text] [PDF]

Home page
 Clin. Chem.Home page
M. R. Snyder and W. E. Highsmith Jr
Commentary
Clin. Chem., August 1, 2008; 54(8): 1399 - 1399.
[Full Text] [PDF]

Home page
 Clin. Chem.Home page
J. Prins, B. B. van der Meijden, R. J. Kraaijenhagen, and J. P.M. Wielders
Inherited Chronic Obstructive Pulmonary Disease: New Selective-Sequencing Workup for {alpha}1-Antitrypsin Deficiency Identifies 2 Previously Unidentified Null Alleles
Clin. Chem., January 1, 2008; 54(1): 101 - 107.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
M. Brantly
Efficient and Accurate Approaches to the Laboratory Diagnosis of {alpha}1-Antitrypsin Deficiency: The Promise of Early Diagnosis and Intervention
Clin. Chem., December 1, 2006; 52(12): 2180 - 2181.
[Full Text] [PDF]

eLetters:

Read all eLetters

Correction of Author List: Diagnosis of á-1-Antitrypsin Deficiency: An Algorithm of Genotyping, Phen
W. Edward Highsmith
Clinical Chemistry Online, 22 May 2007 [Full text]

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Association for Clinical Chemistry.