Return of genetic results in the familial dilated cardiomyopathy research project.

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.

Family history of dilated cardiomyopathy among patients with heart failure from the HF-ACTION genetic ancillary study.

BACKGROUND: The value of family history (FH) is well established, but its sensitivity to detect familial dilated cardiomyopathy (FDC) has been infrequently examined. METHODS: A genetic ancillary study was created as a component of the HF-ACTION trial, a multicenter, prospective, randomized clinical trial of exercise in patients with heart failure and an ejection fraction <35%. A FH-based study using a structured questionnaire mailed to all consenting individuals was incorporated into the genetic ancillary. FH responses were analyzed for dilated cardiomyopathy (DCM) in family members. RESULTS: Of the 741 individuals with data available, 358 (48.3%) had nonischemic and 383 (51.6%) had ischemic etiology, and of these 164 (45.8%) and 201 (52.4%), respectively, returned evaluable questionnaires. Of those with nonischemic etiology, 14/164 (8.5%) reported at least one first-degree family member with DCM or an enlarged heart; another 21/164 (12.8%) reported a FH of "cardiomyopathy," a less specific term to indicate DCM. CONCLUSION: At least 8.5% of patients with nonischemic etiology in the HF-ACTION genetic ancillary study provided FH indicating familial DCM, information important to inform further genetic analyses of this cohort and to plan other studies.