Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study.

Autor: Hart MR; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA. hartmr@uw.edu.; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA. hartmr@uw.edu., Biesecker BB; Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Blout CL; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Christensen KD; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Amendola LM; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA.; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA., Bergstrom KL; Department of Pediatrics, Oncology Section, Baylor College of Medicine, Houston, TX, USA., Biswas S; Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Bowling KM; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Brothers KB; Department of Pediatrics, University of Louisville, Louisville, KY, USA., Conlin LK; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cooper GM; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Dulik MC; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., East KM; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Everett JN; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA., Finnila CR; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Ghazani AA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Gilmore MJ; Department of Medical Genetics, Kaiser Permanente Northwest, Portland, OR, USA., Goddard KAB; Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA., Jarvik GP; Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA.; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA., Johnston JJ; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Kauffman TL; Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA., Kelley WV; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Krier JB; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Lewis KL; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., McGuire AL; Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, USA., McMullen C; Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA., Ou J; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA., Plon SE; Department of Pediatrics, Oncology Section, Baylor College of Medicine, Houston, TX, USA., Rehm HL; Harvard Medical School, Boston, MA, USA.; Laboratory for Molecular Medicine, Partners HealthCare, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Richards CS; Knight Diagnostic Laboratories, Oregon Health Science University, Portland, OR, USA., Romasko EJ; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital, Philadelphia, PA, USA., Miren Sagardia A; Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Spinner NB; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital, Philadelphia, PA, USA., Thompson ML; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Turbitt E; Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Vassy JL; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; VA Boston Healthcare System, Boston, MA, USA., Wilfond BS; Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, WA, USA., Veenstra DL; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA.; Department of Pharmacy, University of Washington, Seattle, WA, USA., Berg JS; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Green RC; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Partners Personalized Medicine, Boston, MA, USA., Biesecker LG; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Hindorff LA; Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. hindorffl@mail.nih.gov.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2019 May; Vol. 21 (5), pp. 1100-1110. Date of Electronic Publication: 2018 Oct 05.
DOI: 10.1038/s41436-018-0308-x
Abstrakt: Purpose: Clinical sequencing emerging in health care may result in secondary findings (SFs).
Methods: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions.
Results: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care.
Conclusion: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.
Databáze: MEDLINE
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