Alpha-1-antitrypsin molecular testing in Canada: A seven year, multi-centre comparison.

Abstract Background Laboratory confirmation of alpha-1-antitrypsin (A1AT) deficiency may be achieved by multiple methods. Here, we compare the relative comprehensiveness and efficiency of pathogenic variant (PV) detection of four different protocols utilized at different diagnostic centres in Canada. Methods Diagnostic results from 2011 to 2018 at clinical laboratories in British Columbia (BC), Alberta (AB), Ontario (ON), and Quebec (QC) were reviewed. The four labs utilize the following protocols: BC-CGID (serum A1AT Concentration/Genotyping/Isoelectric focussing (IEF)/SERPINA1 DNA sequencing), AB-CID (serum A1AT Concentration/IEF/DNA sequencing), ON-CD (serum A1AT Concentration/DNA sequencing), and QC-G (Genotyping). As the respective catchment areas varied in size and ethnic composition, the comprehensiveness of PV detection was assessed by comparing the frequency of individual genotypes to the ZZ genotype, which is clearly identified by all protocols. Results Collectively 5399 index patients were tested identifying 396 ZZ genotypes. Serum A1AT concentration as a determinant of further testing efficiently identified PV. ON-CD had the highest detection rate for PV; genotypes with at least one PV, other than S, Z or F, were identified at 0.67/ZZ as compared to Conclusion Strategies which readily detect variants across the full coding sequence of SERPINA1 detect more PV as well as more UMV and LBV.