Return of Genetic Results in the Familial Dilated Cardiomyopathy Research Project
- 572 Downloads
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.
KeywordsDilated cardiomyopathy Genetics Family studies Return of results Genetic counseling
We thank the more than 2000 probands and family members who have participated in our research program and the many professionals who have referred families to us, without whom this study would not be possible. We thank Katrina Abril and Chad Brodt for their assistance in the data preparation and analysis. This work was supported by an award from the National Institutes of Health (RO1-HL58626, Dr Hershberger).
The authors declare no conflicts of interest of any kind with this work.
- Ackerman, M. J., Priori, S. G., Willems, S., Berul, C., Brugada, R., Calkins, H., et al. (2011). HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies This document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm, 8(8), 1308–1339.PubMedCrossRefGoogle Scholar
- Bookman, E. B., Langehorne, A. A., Eckfeldt, J. H., Glass, K. C., Jarvik, G. P., Klag, M., et al. (2006). Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. American Journal of Medical Genetics. Part A, 140(10), 1033–1040.PubMedCrossRefGoogle Scholar
- Cowan, J., Li, D., Gonzalez-Quintana, J., Morales, A., & Hershberger, R. E. (2010). Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy. Circulation. Cardiovascular Genetics, 3(1), 6–14.PubMedCrossRefGoogle Scholar
- Crispell, K. A., Wray, A., Ni, H., Nauman, D. J., & Hershberger, R. E. (1999). Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: preliminary recommendations for clinical practice. Journal of the American College of Cardiology, 34(3), 837–847.PubMedCrossRefGoogle Scholar
- Fabsitz, R. R., McGuire, A., Sharp, R. R., Puggal, M., Beskow, L. M., Biesecker, L. G., et al. (2010). Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circulation. Cardiovascular Genetics, 3(6), 574–580.PubMedCrossRefGoogle Scholar
- Gollob, M. H., Blier, L., Brugada, R., Champagne, J., Chauhan, V., Connors, S., et al. (2011). Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper. Canadian Journal of Cardiology, 27(2), 232–245.PubMedCrossRefGoogle Scholar
- Hershberger, R. E., Hanson, E., Jakobs, P. M., Keegan, H., Coates, K., Bousman, S., et al. (2002). A novel lamin A/C mutation in a family with dilated cardiomyopathy, prominent conduction system disease, and need for permanent pacemaker implantation. American Heart Journal, 144(6), 1081–1086.PubMedCrossRefGoogle Scholar
- Hershberger, R. E., Cowan, J., & Morales, A. (2008a). LMNA-related dilated cardiomyopathy. http://www.genetests.org.
- Hershberger, R. E., Parks, S. B., Kushner, J. D., Li, D., Ludwigsen, S., Jakobs, P., et al. (2008b). Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clinical Translational Science, 1(1), 21–26.CrossRefGoogle Scholar
- Hershberger, R. E., Cowan, J., Morales, A., & Siegfried, J. D. (2009a). Progress with genetic cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation. Heart Failure, 2(3), 253–261.PubMedCrossRefGoogle Scholar
- Hershberger, R. E., Norton, N., Morales, A., Li, D., Siegfried, J. D., & Gonzalez-Quintana, J. (2010b). Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circulation. Cardiovascular Genetics, 3(2), 155–161.PubMedCrossRefGoogle Scholar
- Meulenkamp, T. M., Gevers, S. J., Bovenberg, J. A., & Smets, E. M. (2011). Researchers' opinions towards the communication of results of biobank research: a survey study. European Journal of Human Genetics.Google Scholar
- Norton, N., Li, D., Reider, M. J., Siegfried, J. D., Rampersaud, E., Zuchner, S., et al. (2011). Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. American Journal of Human Genetics, 88, 273–282.PubMedCrossRefGoogle Scholar
- Rope, A. F., Wang, K., Evjenth, R., Xing, J., Johnston, J. J., Swensen, J. J., et al. (2011). Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency. American Journal of Human Genetics, 89(1), 28–43.PubMedCrossRefGoogle Scholar