The Ophthalmic Experience: Unanticipated Primary Findings in the Era of Next Generation Sequencing
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NEXT GENERATION GENETIC COUNSELING
The Ophthalmic Experience: Unanticipated Primary Findings in the Era of Next Generation Sequencing Jillian T. Huang & John R. Heckenlively & K. Thiran Jayasundera & Kari E. Branham
Received: 30 June 2013 / Accepted: 2 December 2013 # National Society of Genetic Counselors, Inc. 2014
Abstract Next generation sequencing (NGS) technology, with the ability to sequence many genomic regions at once, can provide clinicians with increased information, in the form of more mutations detected. Discussions on broad testing technology have largely been focused on incidental findings, or unanticipated results related to diseases beyond the primary indication for testing. By examining multiple genes that could be responsible for the patient’s presentation, however, there is also the possibility of unexpected results that are related to the reason genetic testing was ordered. We present a case study where multiple potentially causative mutations were detected using NGS technology. This case raises questions of scientific uncertainty, and has important implications for medical management and secondary studies. Clinicians and genetic counselors should be aware of the potential for increased information to affect one’s understanding of genetic risk, and the preand post-testing counseling process. Keywords Ophthalmology . Retinal dystrophy . Genetic testing . Genetic counseling
Introduction Next generation sequencing (NGS) is expanding clinicians’ ability to search for and identify causative mutations for genetic diseases. These sequencing technologies allow for the simultaneous sequencing of large numbers of genomic regions, and so genetic testing strategies are expanding from examining a single gene, to a panel of genes, to the whole J. T. Huang (*) : J. R. Heckenlively : K. T. Jayasundera : K. E. Branham Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall St, 7115 Brehm Tower, Ann Arbor, MI 48105, USA e-mail: [email protected]
exome, and finally, the whole genome. The wealth of genetic information that can be produced from this technology presents new dilemmas and poses additional risks when NGS is applied in a clinical diagnostic setting. Much of the discussion surrounding NGS has focused on the implications of secondary, or incidental, findings, defined as genetic variants that are known or suspected to be pathogenic, but that confer risk of diseases unrelated to the reason that genetic testing was ordered (Raffan and Semple 2011). These are genetic results that neither the clinician nor the patient anticipated when the test was ordered (Wolf et al. 2008). However, next generation sequencing also has the possibility to provide unanticipated results that are highly relevant to the patient’s clinical diagnosis. With NGS, multiple genes are sequenced at once, which can result in the identification of pathogenic mutations in more than one gene. Prior to NGS, finding a potentially pathogenic mutation in one gene may have ended the search for a
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