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. 2023 Mar;103(3):288-300.
doi: 10.1111/cge.14262. Epub 2022 Nov 29.

Bridging clinical care and research in Ontario, Canada: Maximizing diagnoses from reanalysis of clinical exome sequencing data

Taila Hartley  1   2 , Élisabeth Soubry  1 , Meryl Acker  3   4 , Matthew Osmond  1 , Madeline Couse  3 , Meredith K Gillespie  1   5 , Yoko Ito  1   2 , Aren E Marshall  1   2 , Gabrielle Lemire  1   2 , Lijia Huang  2   5 , Caitlin Chisholm  5 , Alison J Eaton  1   2   6 , E Magda Price  1 , James J Dowling  3   4 , Arun K Ramani  3 , Roberto Mendoza-Londono  3   4 , Gregory Costain  3   4 , Michelle M Axford  3   4 , Anna Szuto  3 , Vanda McNiven  3   7 , Nadirah Damseh  3 , Rebekah Jobling  3 , Leanne de Kock  1 , Bahareh A Mojarad  3 , Ted Young  3   4 , Zhuo Shao  4   8 , Robin Z Hayeems  4 , Ian D Graham  2   9 , Mark Tarnopolsky  10 , Lauren Brady  10 , Christine M Armour  2   5 , Michael Geraghty  5 , Julie Richer  2   5 , Sarah Sawyer  2   5 , Matthew Lines  2   5 , Saadet Mercimek-Andrews  3   6 , Melissa T Carter  2   5 , Gail Graham  2   5 , Peter Kannu  3   6 , Joanna Lazier  2   5 , Chumei Li  10 , Ritu B Aul  3   4 , Tugce B Balci  11 , Nomazulu Dlamini  3 , Lauren Badalato  12 , Andrea Guerin  12 , Jagdeep Walia  12 , David Chitayat  3   13 , Ronald Cohn  3 , Hanna Faghfoury  7 , Cynthia Forster-Gibson  14 , Hernan Gonorazky  3 , Eyal Grunebaum  3 , Michal Inbar-Feigenberg  3 , Natalya Karp  11 , Chantal Morel  7 , Alison Rusnak  5   12 , Neal Sondheimer  3 , Jodi Warman-Chardon  1   2   5   15 , Priya T Bhola  2   5 , Danielle K Bourque  2   5 , Inara J Chacon  3 , Lauren Chad  3   4 , Pranesh Chakraborty  1   2   5 , Karen Chong  13 , Asif Doja  2   5 , Elaine Suk-Ying Goh  14 , Maha Saleh  11 ; Care4Rare Canada; Beth K Potter  1   2 , Christian R Marshall  3   4 , David A Dyment  1   2   5 , Kristin Kernohan  1   2   5 , Kym M Boycott  1   2   5
Affiliations

Bridging clinical care and research in Ontario, Canada: Maximizing diagnoses from reanalysis of clinical exome sequencing data

Taila Hartley et al. Clin Genet. 2023 Mar.

Abstract

We examined the utility of clinical and research processes in the reanalysis of publicly-funded clinical exome sequencing data in Ontario, Canada. In partnership with eight sites, we recruited 287 families with suspected rare genetic diseases tested between 2014 and 2020. Data from seven laboratories was reanalyzed with the referring clinicians. Reanalysis of clinically relevant genes identified diagnoses in 4% (13/287); four were missed by clinical testing. Translational research methods, including analysis of novel candidate genes, identified candidates in 21% (61/287). Of these, 24 families have additional evidence through data sharing to support likely diagnoses (8% of cohort). This study indicates few diagnoses are missed by clinical laboratories, the incremental gain from reanalysis of clinically-relevant genes is modest, and the highest yield comes from validation of novel disease-gene associations. Future implementation of translational research methods, including continued reporting of compelling genes of uncertain significance by clinical laboratories, should be considered to maximize diagnoses.

Keywords: exome sequencing; healthcare system; matchmaking; rare disease; reanalysis.

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References

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