Genetic Screening of a Large Panel of Genes Associated with Cardiac Disease in a Spanish Heart Transplanted Cohort

Abstract

In this study we performed a next generation sequencing of 210 genes in 140 patients with cardiac failure requiring a heart transplantation. We identified a total of 48 candidate variants in 47 patients. Forty-three patients (90%) presented a single variant, and fourpatients (10%) were carriers of two variants. After refining the classification, we identified a pathogenic or likely pathogenic variant in 13 patients (10% of our cohort). In 34 additional cases (25%) the variants were classified as of unknown significance (VUS). In reference to the cause of cardiac failure in the 13 carriers of pathogenic variants, 5 were of dilated non-ischemic cause, 4 hypertrophic and 1 restrictive cardiomyopathy. In the ischemic cases (n = 3) no family history of cardiac disease was recorded, while nineof the non-ischemic had other relatives who were also diagnosed. In conclusion, the NGS of a cardiac transplanted cohort identified a definite or very likely genetic cause in 10% of the cases. Most of them had a family history of cardiac disease, and were thus previously studied as part of a routine screening by a genetic counselor. Pathogenic variants in cases without a family history of cardiac disease were mainly of ischemic origin.

Keywords

• heart failure
• heart transplant
• familial cardiomyopathy
• genetic screening