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=Volume 14 - 2023

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=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. We applied a reanalysis strategy based on intensive prospective bibliographic monitoring, and directly applied the Globally search for a Regular Expression and Print matching lines (GREP) command-line tool to a large ES database. For 18 months, we submitted daily the same 5 keywords of interest ((intellectual disability, (neuro)developmental delay, (neuro)developmental disorder)) to PubMed, to identify recently published, novel disease-gene associations, or new phenotypes in genes already implicated in human pathology. We used the Linux GREP query and an inhouse script, to collect all variants in these genes from our 5459 exome database. After GREP queries and variants filtration, we obtained 128 genes and collected 56 candidate variants in 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, the GREP queries of only 128 genes during a period of 18 months permitted to establish a causal diagnosis in 21/2875 undiagnosed affected probands (0.7%). The GREP query is efficient, and less tedious than complete periodical reanalysis. It is an interesting reanalysis strategy to improve diagnosis.