Details

Autor(en) / Beteiligte

• Cuenca, Sofia, MD
• Ruiz-Cano, Maria J., MD, PhD
• Gimeno-Blanes, Juan Ramón, MD, PhD
• Jurado, Alfonso, MD
• Salas, Clara, MD
• Gomez-Diaz, Iria, BSc
• Padron-Barthe, Laura, PhD
• Grillo, Jose Javier, MD
• Vilches, Carlos, MD, PhD
• Segovia, Javier, MD, PhD
• Pascual-Figal, Domingo, MD, PhD
• Lara-Pezzi, Enrique, PhD
• Monserrat, Lorenzo, MD, PhD
• Alonso-Pulpon, Luis, MD, PhD
• Garcia-Pavia, Pablo, MD, PhD

Titel

Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation

Ist Teil von

• The Journal of heart and lung transplantation, 2016-05, Vol.35 (5), p.625-635

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting. Methods Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies. Results Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%). Conclusions The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases.