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

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

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1122985

DOI=10.3389/fgene.2023.1122985

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Patients and methods:</bold> 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 [(<italic>intellectual disability</italic>, (<italic>neuro</italic>)<italic>developmental delay</italic>, and (<italic>neuro</italic>)<italic>developmental disorder</italic>)] 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.</p><p><bold>Results:</bold> 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%).</p><p><bold>Conclusion:</bold> The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis.</p>