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Microbiol Spectr . SARS-CoV-2 N Gene G29195T Point Mutation May Affect Diagnostic Reverse Transcription-PCR Detection

tetano

Editor, Senior Moderator
Microbiol Spectr


. 2022 Jan 12;e0222321.
doi: 10.1128/spectrum.02223-21. Online ahead of print.
SARS-CoV-2 N Gene G29195T Point Mutation May Affect Diagnostic Reverse Transcription-PCR Detection


Karrie K K Ko[SUP] 1 2 3 4 5 [/SUP], Nurdyana Binte Abdul Rahman[SUP] 1 5 [/SUP], Shireen Yan Ling Tan[SUP] 1 5 [/SUP], Kenneth X L Chan[SUP] 2 [/SUP], Sui Sin Goh[SUP] 1 [/SUP], James Heng Chiak Sim[SUP] 1 5 [/SUP], Kun Lee Lim[SUP] 2 [/SUP], Wan Loo Tan[SUP] 2 [/SUP], Kian Sing Chan[SUP] 2 5 [/SUP], Lynette L E Oon[SUP] 2 5 [/SUP], Niranjan Nagarajan[SUP] 3 4 [/SUP], Chayaporn Suphavilai[SUP] 3 [/SUP]



Affiliations

Abstract

Rapid onsite whole-genome sequencing of two suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene diagnostic escape samples revealed a previously unreported N gene point mutation at genome position 29195. Because the G29195T mutation occurs within a region probed by a commonly referenced U.S. CDC N gene reverse transcription (RT)-PCR assay, we hypothesize that the G29195T mutation rendered the N gene target of a proprietary commercial assay undetectable. The putative diagnostic escape G29195T mutation demonstrates the need for nearly real-time surveillance, as emergence of a novel SARS-CoV-2 variant with the potential to escape diagnostic tests continues to be a threat. IMPORTANCE Accurate diagnostic detection of SARS-CoV-2 currently depends on the large-scale deployment of RT-PCR assays. SARS-CoV-2 RT-PCR assays target predetermined regions in the viral genomes by complementary binding of primers and probes to nucleic acid sequences in the clinical samples. Potential diagnostic escapes, such as those of clinical samples harboring the G29195T mutation, may result in false-negative SARS-CoV-2 RT-PCR results. The rapid detection and sharing of potential diagnostic escapes are essential for diagnostic laboratories and manufacturers around the world, to optimize their assays as SARS-CoV-2 continues to evolve.

Keywords: G29195T; N gene; SARS-CoV-2; diagnostic escape.
 
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