Frontiers in Genetics (Apr 2023)

Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis

  • Frédéric Tran Mau-Them,
  • Frédéric Tran Mau-Them,
  • Alexis Overs,
  • Ange-Line Bruel,
  • Ange-Line Bruel,
  • Romain Duquet,
  • Mylene Thareau,
  • Anne-Sophie Denommé-Pichon,
  • Anne-Sophie Denommé-Pichon,
  • Antonio Vitobello,
  • Antonio Vitobello,
  • Arthur Sorlin,
  • Arthur Sorlin,
  • Hana Safraou,
  • Hana Safraou,
  • Sophie Nambot,
  • Julian Delanne,
  • Sebastien Moutton,
  • Caroline Racine,
  • Camille Engel,
  • Melchior De Giraud d’Agay,
  • Daphne Lehalle,
  • Alice Goldenberg,
  • Alice Goldenberg,
  • Marjolaine Willems,
  • Christine Coubes,
  • David Genevieve,
  • Alain Verloes,
  • Alain Verloes,
  • Yline Capri,
  • Laurence Perrin,
  • Marie-Line Jacquemont,
  • Laetitia Lambert,
  • Elodie Lacaze,
  • Julien Thevenon,
  • Nadine Hana,
  • Nadine Hana,
  • Julien Van-Gils,
  • Charlotte Dubucs,
  • Varoona Bizaoui,
  • Marion Gerard-Blanluet,
  • James Lespinasse,
  • Sandra Mercier,
  • Anne-Marie Guerrot,
  • Anne-Marie Guerrot,
  • Isabelle Maystadt,
  • Emilie Tisserant,
  • Laurence Faivre,
  • Laurence Faivre,
  • Christophe Philippe,
  • Christophe Philippe,
  • Yannis Duffourd,
  • Yannis Duffourd,
  • Christel Thauvin-Robinet,
  • Christel Thauvin-Robinet,
  • Christel Thauvin-Robinet

DOI
https://doi.org/10.3389/fgene.2023.1122985
Journal volume & issue
Vol. 14

Abstract

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Introduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories.Patients and methods: We applied a reanalysis strategy based on intensive prospective bibliographic monitoring along with direct application of the GREP command-line tool (to “globally search for a regular expression and print matching lines”) in a large ES database. For 18 months, we submitted the same five keywords of interest [(intellectual disability, (neuro)developmental delay, and (neuro)developmental disorder)] to PubMed on a daily basis to identify recently published novel disease–gene associations or new phenotypes in genes already implicated in human pathology. We used the Linux GREP tool and an in-house script to collect all variants of these genes from our 5,459 exome database.Results: After GREP queries and variant filtration, we identified 128 genes of interest and collected 56 candidate variants from 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, GREP queries for only 128 genes over a period of 18 months permitted a causal diagnosis to be established in 21/2875 undiagnosed affected probands (0.7%).Conclusion: The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis.

Keywords