Incidental findings in genetic research and clinical diagnostic tests: A systematic review

School of Nursing and Midwifery, Plymouth University, Plymouth, UK. .
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 12/2012; 158A(12). DOI: 10.1002/ajmg.a.35615
Source: PubMed

ABSTRACT Incidental findings arise when clinically relevant genetic information about a research participant or patient is identified outside the scope of the original research objective or diagnostic test being performed. These findings can relate to carrier status for a heritable condition, misattributed paternity or increased susceptibility to a medical condition. The decision whether to disclose these findings to the research subject or patient is underpinned by many ethical, moral, and potentially legal considerations. There is an urgent need for definitive guidelines for researchers and healthcare professionals. We performed a systematic review of the relevant literature concerning the disclosure of incidental findings, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, using the prescribed flowchart and checklist. At initial screening, 473 articles were retrieved. The inclusion and exclusion criteria aimed at obtaining data that were relevant and of sufficient quality were applied and a total of four relevant studies were identified, comprising 2,680 individual participants and 1,023 guidance documents. Major themes emerging from the included articles include patient autonomy, patient welfare, harmful secrets, and genetic literacy. The lack of relevant studies emphasizes the urgent need for empirical investigations into the disclosure or non-disclosure of genetic incidental findings, and the provision of guidelines to assist healthcare professionals and researchers. © 2012 Wiley Periodicals, Inc.

Download full-text


Available from: Leigh Jackson, Jul 05, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High-throughput nucleotide sequencing (often referred to as next generation sequencing) is increasingly being chosen as a diagnostic tool for cases of expected but unresolved genetic origin. When exploring a higher number of genetic variants, there is a higher chance of detecting unsolicited findings. The consequential increased need for decisions on disclosure of these unsolicited findings poses a challenge for the informed consent procedure. This article discusses the ethical and practical dilemmas encountered when contemplating informed consent for next generation sequencing in diagnostics from a multidisciplinary point of view. By exploring recent similar experiences with unsolicited findings in other settings an attempt is made to describe what can be learned so far for implementing next generation sequencing in standard genetic diagnostics. The article concludes with a set of points to consider in order to guide decision-making on the extent of return of results in relation to the mode of informed consent. We hereby aim to provide a sound basis for developing guidelines for optimizing the informed consent procedure. This article is protected by copyright. All rights reserved.
    Human Mutation 10/2013; 34(10). DOI:10.1002/humu.22370 · 5.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genome-wide research that explores the genetic basis of a specific phenotype has the potential to incidentally uncover data relating to other existing and potential future phenotypes. It is vitally important to explore the ethical implications of these technologies and understand how research participants, lay members of the public, genomic researchers and health professionals wish to utilize this new information. We describe a new study to gather large-scale empirical data on what genetic results should be shared with research participants taking part in whole genome research. Whole genome studies, by virtue of involving all 20,000þ genes, inevitably produce large volumes of genetic data some of which will be of actual or potential clinical significance. Whilst some of this data will be directly " pertinent " to the phenotype under study (e.g., a child's developmental disorder), others are likely to be " incidental " in that they are completely unrelated to the phenotype being investigated. What should be done with this data and what might research participants want to know? A systematic review of research about these very issues revealed a " lack of relevant studies " and an " urgent need for empirical investigations in the disclosure or non-disclosure of genetic incidental findings " [Jackson et al., 2012]. The Deciphering Developmental Disorders (DDD) project is using genome-wide approaches to investigate $12,000 children with severe undiagnosed developmental disorders. Research samples from probands and their parents are being collected from every Regional Genetics Service in the UK and Republic of Ireland [Firth and Wright, 2011]. Samples are sent to the Wellcome Trust Sanger Institute where high-resolution genomic techniques including array-CGH and exome sequencing are being used to identify genetic causes for such developmental disorders. Results that are likely to be etiologically relevant and pertinent to the child's phenotype are shared with the clinical center; incidental findings are not shared. There is evidence to suggest that research participants in genetics studies want to receive pertinent findings relating to the medical condition under study [Wendler and Emanuel, 2002]. However, little is known about what research participants think about incidental findings, including clinically significant information relating to medical conditions unrelated to the disorder under study. There is much discussion in the medical, ethics, genetics and social sciences literature about the merits and pitfalls of sharing genomic information in a research and clinical setting [
    American Journal of Medical Genetics 08/2013; 161(8). DOI:10.1002/ajmg.a.36067 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human germline mutations arise anew during meiosis in every generation. Such spontaneously occurring genetic variants are termed de novo mutations. Although the introduction of microarray based approaches led to the discovery of numerous de novo copy number variants underlying a range of human genetic conditions, de novo single nucleotide variants (SNVs) remained refractory to analysis at the whole genome level until the advent of next generation sequencing technologies such as whole genome sequencing and whole exome sequencing. These approaches have recently allowed the estimation of the mutation rate of de novo SNVs and greatly increased our understanding of their contribution to human genetic disease. Indeed, de novo SNVs have been found to underlie various common human neurodevelopmental conditions such as schizophrenia, autism and intellectual disability, as well as sporadic cases of rare Mendelian disorders. In many cases, however, confirmation of the pathogenicity of identified de novo SNVs remains a major challenge.
    Journal of Medical Genetics 02/2013; 50(4). DOI:10.1136/jmedgenet-2013-101519 · 5.64 Impact Factor