학술논문
Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests
Document Type
Article
Author
Thauvin-Robinet, Christel; Thevenon, Julien; Nambot, Sophie; Delanne, Julian; Kuentz, Paul; Bruel, Ange-Line; Chassagne, Aline; Cretin, Elodie; Pelissier, Aurore; Peyron, Chritine; Gautier, Elodie; Lehalle, Daphné; Jean-Marçais, Nolwenn; Callier, Patrick; Mosca-Boidron, Anne-Laure; Vitobello, Antonio; Sorlin, Arthur; Tran Mau-Them, Frédéric; Philippe, Christophe; Vabres, Pierre; Demougeot, Laurent; Poé, Charlotte; Jouan, Thibaud; Chevarin, Martin; Lefebvre, Mathilde; Bardou, Marc; Tisserant, Emilie; Luu, Maxime; Binquet, Christine; Deleuze, Jean-François; Verstuyft, Céline; Duffourd, Yannis; Faivre, Laurence
Source
European Journal of Human Genetics: EJHG; August 2019, Vol. 27 Issue: 8 p1197-1214, 18p
Subject
Language
ISSN
10184813; 14765438
Abstract
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 (CYP2C9and 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.