Return of Genetic Results in the Familial Dilated Cardiomyopathy Research Project
Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL, USA.Journal of Genetic Counseling (Impact Factor: 2.24). 08/2012; 22(2). DOI: 10.1007/s10897-012-9532-8
The goal of the Familial Dilated Cardiomyopathy (FDC) Research Project, initiated in 1993, has been to identify and characterize FDC genetic cause. All participating individuals have been consented for the return of genetic results, an important but challenging undertaking. Since the inception of the Project we have enrolled 606 probands, and 269 of these had 1670 family members also enrolled. Each subject was evaluated for idiopathic dilated cardiomyopathy (IDC) and pedigrees were categorized as familial or sporadic. The coding regions of 14 genes were resequenced in 311 to 324 probands in five studies. Ninety-two probands were found to carry nonsynonymous rare variants absent in controls, and with Clinical Laboratory Improvement Amendment of 1988 (CLIA) compliant protocols, relevant genetic results were returned to these probands and their consented relatives by study genetic counselors and physicians in 353 letters. In 10 of the 51 families that received results >1 year ago, at least 23 individuals underwent CLIA confirmation testing for their family's rare variant. Return of genetic results has been successfully undertaken in the FDC Research Project. This report describes the methods utilized in the process of returning research results. We use this information as a springboard for providing guidance to other genetic research groups and proposing future directions in this arena.
Article: Familial dilated cardiomyopathy[Show abstract] [Hide abstract]
ABSTRACT: Familial dilated cardiomyopathy (F-DCM) describes a clinically and genetically heterogeneous group of diseases, mostly inherited as autosomal dominant traits, having idiopathic left ventricular dilatation and dysfunction as a common phenotype. The age of onset, rate of progression, disease complications, as well as overall prognosis and outcome vary both amongst and within families. Clinical traits, both cardiac and extracardiac, may recur in association with the DCM phenotype. The former include conduction defects, structural abnormalities such as left ventricular noncompaction, of right ventricular involvement, and recurrence of atrial or ventricular arrhythmias; the latter commonly affect the musculoskeletal (myopathies/dystrophies, both clinically overt and subclinical), ocular, auditory, nervous, and integument systems. These traits may help guide genetic testing. In parallel to the clinical heterogeneity, F-DCM also shows genetic heterogeneity: more than 40 genes have been causally linked to F-DCM, with mutations recurring more commonly in a few known genes, and less frequently in rare, less commonly known genes. Based on the known prevalence of mutations in disease genes, more than 50% of F-DCM cases can be regarded as still genetically orphan, implying that further disease genes have to be discovered. Family screening and genetic testing are now established as the gold standard for diagnosis, care, and prevention in F-DCM. Diagnostic tests are performed using Sanger-based sequencing. Furthermore, new biotechnology tools, based on next-generation sequencing, are now being implemented in the research setting and will dramatically modify the future of the nosology of F-DCM.
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ABSTRACT: While the disclosure of research findings is relevant to all types of biomedical research, it has garnered particular attention with respect to genetics and genomics research due to some of the unique aspects of the data and the high public profile of the field. In this chapter, we review the attitudes of stakeholders (research participants, policymakers, and researchers) to define areas of consensus regarding the issue of returning research results across and within groups. In addition to stakeholder attitudes about obligations and interest in research results, other major related issues related to returning research results, such as informed consent, communication of research results, and cost, are discussed. Given the consensus between stakeholders to return summary reports of a study's outcomes and individual research results of clinical significance, we conclude that the time has come to encourage, if not require, researchers to consider these issues in the developmental planning stages of a project and to plan and budget accordingly.
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ABSTRACT: Background: Although research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants' experiences. To address this, we developed and deployed a survey at 15 NIH-supported clinical research centers to assess participant-centered outcomes; we report responses from 4,961 participants. Methods: Survey questions addressed core aspects of the research participants' experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses. Results: Respondents broadly represented the research population in sex, race, and ethnicity. Seventy-three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R(2) = 0.80-0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%). Conclusions: Our survey demonstrates that a majority of participants at NIH-supported clinical research centers rate their research experience very positively and that participant-centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.
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