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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 Québec (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 <0.2/ZZ (all others). However, ON-CD had the highest rates of undefined molecular variants (UMV) (0.16/ZZ) or likely benign variants (LBV) (0.08/ZZ), compared to all others (<0.12/ZZ and < 0.06/ZZ, respectively). The F variant was identified at 0.10/ZZ, only in the ON-CD and the AB-CID protocols. Collectively, MMalton was the next most common variant, identified as a compound heterozygous genotype at 0.04/ZZ, only in the ON-CD and BC-CGID protocols. CONCLUSION:Strategies which readily detect variants across the full coding sequence of SERPINA1 detect more PV as well as more UMV and LBV.

journal_name

Clin Biochem

journal_title

Clinical biochemistry

authors

Mattman A,Gilfix BM,Chen SX,DeMarco ML,Kyle BD,Parker ML,Agbor TA,Jung B,Selvarajah S,Barakauskas VE,Vaags AK,Estey MP,Nelson TN,Speevak MD

doi

10.1016/j.clinbiochem.2020.05.001

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

27-33

eissn

0009-9120

issn

1873-2933

pii

S0009-9120(20)30076-X

journal_volume

pub_type

杂志文章,多中心研究

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