title: Current Practices and the Provider Perspectives on Inconclusive Genetic Test Results for Osteogenesis Imperfecta in Children with Unexplained Fractures: ELSI Implications.
abstract: Genetic testing can be used to determine if unexplained fractures in children could have resulted from a predisposition to bone fractures, e.g., osteogenesis imperfecta. However, uncertainty is introduced if a variant of unknown significance (VUS) is identified. Proper interpretation of VUS in these situations is critical because of its influence on clinical care and in court rulings. This study sought to understand how VUS are interpreted and used by practitioners when there is a differential diagnosis including both osteogenesis imperfecta and non-accidental injury.A 15-question survey was emailed to physicians who requested analysis of two genes, COL1A1 and COL1A2, from the University of Washington from 2005-2013 for patient cases involving suspicion of child abuse.Among the 89 participants, responses differed about when genetic testing should be ordered for osteogenesis imperfecta, who should be consulted about utilization of VUS test results, follow-up procedures, and who should receive the VUS results.There are no clear guidelines for how to interpret and follow up on VUS. In the legal setting, misinterpreted VUS could lead to unintended consequences and deleterious ramifications for family members. The need for better practice guidelines to help promote more equitable handling of these sensitive legal cases is clear.
authors: Emily Youngblom, M.P.H., is a Ph.D. candidate at the Institute of Public Health Genetics at the University of Washington. She completed her undergraduate degree at the University of California-Berkeley (Berkeley, CA) and her M.P.H. in Public Health Genetics at the University of Washington (Seattle, WA). Mitzi Leah Murray, M.D., M.A., is a clinical geneticist with a focus on evaluating and providing care for individuals and families with heritable connective tissue disorders. She is also the assistant director of the Collagen Diagnostic Laboratory at the University of Washington. Dr. Murray earned her undergraduate degree from Ohio University (Athens, OH), her medical degree from the University of Texas Southwestern Medical School (Dallas, TX), her Masters of Bioethics from the University of Washington (Seattle, WA), and is board certified in clinical genetics and in clinical molecular genetics. Peter H. Byers, M.D., is a clinical geneticist with the focus of understanding the molecular pathogenesis of inherited disorders of connective tissue. He is currently the director of both the Collagen Diagnostic Laboratory and the Center for Precision Diagnostics at the University of Washington. Dr. Byers earned his undergraduate degree from Reed College (Portland, OR), his medical degree from Case Western Reserve University (Cleveland, OH), and completed residency at the University of California-San Francisco (San Francisco, CA). He is board certified by both the American Board of Medical Genetics and the American Board of Internal Medicine.
authors: Emily
authors: E
authors: Youngblom
authors: Emily Youngblom, M.P.H., is a Ph.D. candidate at the Institute of Public Health Genetics at the University of Washington. She completed her undergraduate degree at the University of California-Berkeley (Berkeley, CA) and her M.P.H. in Public Health Genetics at the University of Washington (Seattle, WA). Mitzi Leah Murray, M.D., M.A., is a clinical geneticist with a focus on evaluating and providing care for individuals and families with heritable connective tissue disorders. She is also the assistant director of the Collagen Diagnostic Laboratory at the University of Washington. Dr. Murray earned her undergraduate degree from Ohio University (Athens, OH), her medical degree from the University of Texas Southwestern Medical School (Dallas, TX), her Masters of Bioethics from the University of Washington (Seattle, WA), and is board certified in clinical genetics and in clinical molecular genetics. Peter H. Byers, M.D., is a clinical geneticist with the focus of understanding the molecular pathogenesis of inherited disorders of connective tissue. He is currently the director of both the Collagen Diagnostic Laboratory and the Center for Precision Diagnostics at the University of Washington. Dr. Byers earned his undergraduate degree from Reed College (Portland, OR), his medical degree from Case Western Reserve University (Cleveland, OH), and completed residency at the University of California-San Francisco (San Francisco, CA). He is board certified by both the American Board of Medical Genetics and the American Board of Internal Medicine.
authors: Mitzi Leah
authors: ML
authors: Murray
authors: Emily Youngblom, M.P.H., is a Ph.D. candidate at the Institute of Public Health Genetics at the University of Washington. She completed her undergraduate degree at the University of California-Berkeley (Berkeley, CA) and her M.P.H. in Public Health Genetics at the University of Washington (Seattle, WA). Mitzi Leah Murray, M.D., M.A., is a clinical geneticist with a focus on evaluating and providing care for individuals and families with heritable connective tissue disorders. She is also the assistant director of the Collagen Diagnostic Laboratory at the University of Washington. Dr. Murray earned her undergraduate degree from Ohio University (Athens, OH), her medical degree from the University of Texas Southwestern Medical School (Dallas, TX), her Masters of Bioethics from the University of Washington (Seattle, WA), and is board certified in clinical genetics and in clinical molecular genetics. Peter H. Byers, M.D., is a clinical geneticist with the focus of understanding the molecular pathogenesis of inherited disorders of connective tissue. He is currently the director of both the Collagen Diagnostic Laboratory and the Center for Precision Diagnostics at the University of Washington. Dr. Byers earned his undergraduate degree from Reed College (Portland, OR), his medical degree from Case Western Reserve University (Cleveland, OH), and completed residency at the University of California-San Francisco (San Francisco, CA). He is board certified by both the American Board of Medical Genetics and the American Board of Internal Medicine.
authors: Peter H
authors: PH
authors: Byers
mesh_terms: D002648:Child; D050723:Fractures, Bone / Q000209:etiology*; D005820:Genetic Testing; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000150:complications*; D010820:Physicians; D011795:Surveys and Questionnaires