RT Journal Article
SR Electronic
T1 New method of Alpha-1-antitrypsin diagnosis facilitates the detection of rare mutations
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2200
DO 10.1183/13993003.congress-2020.2200
VO 56
IS suppl 64
A1 Andreas Klemmer
A1 Martina Veith
A1 Julia Tüffers
A1 Erika Peychev
A1 Christoph Berndt
A1 Viktor Kotke
A1 Christian Herr
A1 Robert Bals
A1 Claus Franz Vogelmeier
A1 Timm Greulich
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/2200.abstract
AB Introduction: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary disease resulting from mutations in the SERPINA1 (serine protease inhibitor) gene and is characterized by low AAT serum levels. Among the more than 100 known mutations of SERPINA1, the Z- and the S-Allele are the most frequent mutations leading to AATD. Different PCR-based methods can be used in laboratory practice.Aims and Objectives: The study provides a comparison of the results (AATD laboratory of the University of Marburg) after the introduction of a new diagnostic genotyping kit (Progenika A1AT Genotyping Test) as compared to the conventional PCR-based algorithm before the introduction of the test.Methods: In July 2016, a new method has been established (Luminex xMAP-based multiplex PCR), allowing the detection of 14 SERPINA1 mutations, while in the time period before July 2016, genotyping was performed with a PCR-analysis for the presence of the S- and Z-mutation only. Isoelectric focusing (IEF) of serum or “dried-blood-spot” (DBS) and/or sequencing was used to diagnose unclear cases. We compared the AAT-genotypes of all 8,137 patients diagnosed by Luminex-based multiplex PCR to the same number of patients before July 2016.Results: Using multiplex PCR, we found 8,056 genotypes without sequencing, including 392 rare (of the 14 mutations) and 68 other (rare or new). In 8,137 individuals, analyzed before the introduction of the new test, only 7,836 could be diagnosed directly, and 301 had to be sequenced (finding 270 rare and 25 new mutations).Conclusion: The introduction of a new Luminex-based multiplex PCR leads to a marked reduction of samples that need to be sequenced, thus simplifies the diagnostic algorithm.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2200.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).