title: Evaluation of an integrative diagnostic algorithm for the identification of people at risk for alpha1-antitrypsin deficiency.
abstract: An integrative diagnostic algorithm for alpha1-antitrypsin (AAT) deficiency testing in the clinical laboratory was developed and evaluated. A novel rapid LightCycler (Roche, Indianapolis, IN) molecular assay was used to detect the common S and Z deficiency allelic variants. However, use of such molecular assays for these variants also can result in the misclassification of significant numbers of "at-risk" patient samples containing other rare AAT deficiency alleles. In the diagnostic algorithm presented herein, patient samples with selected genotypes that exhibit abnormally low AAT concentrations by immunoassay are phenotyped by isoelectric focusing. To test the efficacy of this algorithm, we retrospectively evaluated a data set of 50,020 serum samples for which protein phenotype and AAT concentration had been determined. This algorithm can successfully detect the majority of at-risk samples containing rare deficiency alleles.
authors: The Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors: Joshua A
authors: JA
authors: Bornhorst
authors: Melinda
authors: M
authors: Procter
authors: Cindy
authors: C
authors: Meadows
authors: Edward R
authors: ER
authors: Ashwood
authors: Rong
authors: R
authors: Mao
mesh_terms: D000465:Algorithms; D000483:Alleles; D019992:Databases as Topic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015203:Reproducibility of Results; D012306:Risk; D000515:alpha 1-Antitrypsin / Q000097:blood* / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis*
chemical_list: D000515:alpha 1-Antitrypsin