Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests.
Christel Thauvin-RobinetJulien ThevenonSophie NambotJulian DelannePaul KuentzAnge-Line BruelAline ChassagneElodie CretinAurore PelissierChritine PeyronElodie GautierDaphné LehalleNolwenn Jean-MarçaisPatrick CallierAnne-Laure Mosca-BoidronAntonio VitobelloArthur SorlinFrédéric Tran Mau-ThemChristophe PhilippePierre VabresLaurent DemougeotCharlotte PoéThibaud JouanMartin ChevarinMathilde LefebvreMarc BardouEmilie TisserantMaxime LuuChristine BinquetJean-François DeleuzeCéline VerstuyftYannis DuffourdLaurence FaivrePublished in: European journal of human genetics : EJHG (2019)
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.
Keyphrases
- copy number
- genome wide
- dna methylation
- healthcare
- genome wide identification
- bioinformatics analysis
- end stage renal disease
- genome wide analysis
- ejection fraction
- newly diagnosed
- palliative care
- primary care
- transcription factor
- small molecule
- gene expression
- peritoneal dialysis
- smoking cessation
- chronic pain
- patient reported outcomes
- pain management
- risk assessment
- social media
- general practice
- young adults
- hepatitis c virus
- adverse drug
- binding protein
- affordable care act
- protein protein