Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals
| Autor: | Frans van Agt, Ilse Feenstra, Femke Tammer, Helger G. Yntema, Han G. Brunner, Anke J M Oerlemans, Lonneke Haer-Wigman, Lisenka E.L.M. Vissers, Martine P A van Koolwijk, Vyne van der Schoot, Yvonne Arens |
|---|---|
| Přispěvatelé: | MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, MUMC+: DA Klinische Genetica (5) |
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
MEDLINE MEDICAL GENETICS Disease AMERICAN-COLLEGE VARIANTS Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] 03 medical and health sciences Genetics medicine Genetics (clinical) Exome sequencing 030304 developmental biology 0303 health sciences Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] business.industry SECONDARY FINDINGS 030305 genetics & heredity 3. Good health Clinical Practice Clinical question Family medicine Medical genetics INCIDENTAL FINDINGS Disease manifestation business Pharmacogenetics |
| Zdroj: | European Journal of Human Genetics, 30(2), 170-177. Nature Publishing Group European Journal of Human Genetics, 30, 170-177 European Journal of Human Genetics, 30, 2, pp. 170-177 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/s41431-021-00964-0 |
| Popis: | Contains fulltext : 248380.pdf (Publisher’s version ) (Open Access) Unsolicited findings (UFs) are uncovered unintentionally and predispose to a disease unrelated to the clinical question. The frequency and nature of UFs uncovered in clinical practice remain largely unexplored. We here evaluated UFs identified during a 5-year period in which 16,482 index patients received clinical whole-exome sequencing (WES). UFs were identified in 0.58% (95/16,482) of index patients, indicating that the overall frequency of UFs in clinical WES is low. Fewer UFs were identified using restricted disease-gene panels (0.03%) than when using whole-exome/Mendeliome analysis (1.03%). The UF was disclosed to 86 of 95 individuals, for reasons of medical actionability. Only 61% of these UFs reside in a gene that is listed on the "ACMG59"-list, representing a list of 59 genes for which the American College of Medical Genetics recommends UF disclosure. The remaining 39% were grouped into four categories: disorders similar to "ACMG59"-listed disorders (25%); disorders for which disease manifestation could be influenced (7%); UFs providing reproductive options (2%); and UFs with pharmacogenetic implications (5%). Hence, our experience shows that UFs predisposing to medically actionable disorders affect a broader range of genes than listed on the "ACMG59", advocating that a pre-defined gene list is too restrictive, and that UFs may require ad hoc evaluation of medical actionability. While both the identification and disclosure of UFs depend on local policy, our lessons learned provide general essential insight into the nature and odds of UFs in clinical exome sequencing. |
| Databáze: | OpenAIRE |
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