title: A Library of Rare α1-Antitrypsin (AAT) Variant Phenotypes to Aid in the Diagnosis of AAT Deficiency.
abstract: OBJECTIVE
  α1-Antitrypsin (AAT) deficiency is a hereditary disorder due to defective production of the serine protease inhibitor, AAT, which can cause lung and liver diseases. Severity of disease depends particularly on the phenotypic representation of AAT variants in the patient.
  
  
  METHODS
  In this study, we present determination of seven common and nine rare variant phenotypes of AAT using pediatric samples collected in Texas Children's Hospital to address the knowledge gap in the identification of rare variants. We tested 16 different AAT variants that had been stored in a -80 °C freezer over the years to add to the reference library of AAT variants. The gold-standard isoelectric focusing electrophoresis method was used for analysis and interpretation of AAT variants. Each variant was inspected visually by comparing multiple bands, unique to phenotypic identity, with a previously identified pattern.
  
  
  RESULTS
  Seven common M, S, and Z variants were identified as M1M1, M2M2, M1M2, MS, SS, SZ, and ZZ. Nine rare variants were identified as FM, FS, FZ, PM, XM, YM, IM, TS, and EP. These were interpreted independently and in a blinded manner by an experienced technologist and two clinical chemists from two different institutions.
  
  
  CONCLUSIONS
  Our results add to the reference library to identify the rare variant phenotypes of AAT protein. This report will guide clinical laboratories for proper assessment of rare variants and in turn contribute to accurate diagnosis and management of AAT deficiency.
authors.affiliation: From the Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX Texas Children's Hospital, Houston.
authors.forename: Neval
authors.initials: N
authors.lastname: Akbas
authors.affiliation: Texas Children's Hospital, Houston.
authors.forename: Graciela
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: From the Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX Texas Children's Hospital, Houston.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Buffone
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City.
authors.forename: David G
authors.initials: DG
authors.lastname: Grenache
authors.affiliation: From the Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX Texas Children's Hospital, Houston sxdevara@texaschildrens.org.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000483:Alleles; D005838:Genotype; D006801:Humans; D007525:Isoelectric Focusing; D010641:Phenotype; D012720:Severity of Illness Index; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis*
chemical_list: D000515:alpha 1-Antitrypsin
keywords: AAT; Electrophoresis; IEF; Isoelectric focusing; Phenotype; Variant; α1-Antitrypsin deficiency