Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• European journal of human genetics : EJHG, 2019-08, Vol.27 (8), p.1197-1214

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.