Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests

Autor: Aurore Pélissier, Anne-Laure Mosca-Boidron, Thibaud Jouan, Elodie Cretin, Maxime Luu, Pierre Vabres, Jean-François Deleuze, Chritine Peyron, Nolwenn Jean-Marçais, Julien Thevenon, Christine Binquet, Frédéric Tran Mau-Them, Ange-Line Bruel, Patrick Callier, Elodie Gautier, Laurent Demougeot, Daphné Lehalle, Christophe Philippe, Paul Kuentz, Martin Chevarin, Sophie Nambot, Aline Chassagne, Charlotte Poe, Christel Thauvin-Robinet, Mathilde Lefebvre, Marc Bardou, Céline Verstuyft, Antonio Vitobello, Laurence Faivre, Julian Delanne, Emilie Tisserant, Arthur Sorlin, Yannis Duffourd
Rok vydání: 2019
Předmět:
Zdroj: Eur J Hum Genet
ISSN: 1476-5438
1018-4813
Popis: With exome/genome sequencing (ES/GS) integrated into the practice of medicine, there is some potential for reporting incidental/secondary findings (IFs/SFs). The issue of IFs/SFs has been studied extensively over the last 4 years. In order to evaluate their implications in care organisation, we retrospectively evaluated, in a cohort of 700 consecutive probands, the frequency and burden of introducing the search for variants in a maximum list of 244 medically actionable genes (genes that predispose carriers to a preventable or treatable disease in childhood/adulthood and genes for genetic counselling issues). We also focused on the 59 PharmGKB class IA/IB pharmacogenetic variants. We also compared the results in different gene lists. We identified variants (likely) affecting protein function in genes for care in 26 cases (3.7%) and heterozygous variants in genes for genetic counselling in 29 cases (3.8%). Mean time for the 700 patients was about 6.3 min/patient for medically actionable genes and 1.3 min/patient for genes for genetic counselling, and a mean time of 37 min/patients for the reinterpreted variants. These results would lead to all 700 pre-test counselling sessions being longer, to 55 post-test genetic consultations and to 27 secondary specialised medical evaluations. ES also detected 42/59 pharmacogenetic variants or combinations of variants in the majority of cases. An extremely low metabolizer status in genes relevant for neurodevelopmental disorders (CYP2C9 and CYP2C19) was found in 57/700 cases. This study provides information regarding the need to anticipate the implementation of genomic medicine, notably the work overload at various steps of the process.
Databáze: OpenAIRE
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