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.

Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients

“…All participants were transplanted in the same reference center for cardiac transplant from 2003 to 2018, Hospital Universitario Central Asturias (HUCA). Most transplanted patients were male (74%), and the mean age of the cohort was 55 years (±9.7 SD) [2]. Patients were of European ancestry and from the region of Asturias, northern Spain (total population, approx.…”

“…DNA was obtained from blood leukocytes by the salting-out method in all patients, and NGS was performed with a 205 cardiovascular-disease-associated gene panel, as previously reported [2]. DNA was sequenced by ion torrent technology using semiconductor chips in an Ion Gene Studio S5 Plus sequencer (Termo Fisher Scientific) according to a previously described procedure [10][11][12][13].…”

“…software. To analyze sequence quality and depth coverage and for variant identification, we used the Integrative Genome Viewer (IGV, Broad Institute) [2].…”

“…Moreover, early identification of asymptomatic relatives may lead to early treatment and prevention of progression to HF and proper genetic counseling [1]. In this regard, our group already performed genetic testing on a cohort of transplanted patients and successfully identified concealed inherited cardiomyopathies such as MCD and hypertrophic cardiomyopathy (MCH) [2]. We found a pathogenic variant in genes associated with MCH and MCD (FLNC, LMNA, MYBPC3, MYH7, TNNT2, and TTN) in nearly 1 out of every 10 transplanted recipients [2].…”

“…This may help in early identification of asymptomatic relatives in which early treatment and prevention strategies, as well as proper genetic counseling, could subsequently be performed [1]. Therefore, in this study, we aimed to evaluate the genetic information in the genes associated with FH in a cohort of heart-transplanted patients who had already undergone genetic testing to identify other underlying inherited cardiomyopathies [2].…”