Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies
Por:
Campuzano O, Fernandez-Falgueras A, Sarquella-Brugada G, César-Díaz S, Arbelo E, García-Álvarez A, Jordà P, Coll M, Fiol JV, Iglesias A, Perez-Serra A, Mates J, Del Olmo B, Ferrer C, Alcalde M, Puigmulé M, Mademont-Soler I, Pico F, Lopez L, Tiron C, Brugada-Terradellas J and Brugada R
Publicada:
15 may 2019
Ahead of Print:
15 may 2019
Resumen:
Cardiomyopathies are a heterogeneous group of inherited cardiac diseases characterized by progressive myocardium abnormalities associated with mechanical and/or electrical dysfunction. Massive genetic sequencing technologies allow a comprehensive genetic analysis to unravel the cause of disease. However, most identified genetic variants remain of unknown clinical significance due to incomplete penetrance and variable expressivity. Therefore, genetic interpretation of variants and translation into clinical practice remain a current challenge. We performed retrospective comprehensive clinical assessment and genetic analysis in six families, four diagnosed with arrhythmogenic cardiomyopathy, and two diagnosed with hypertrophic cardiomyopathy (HCM). Genetic testing identified three rare variants (two non-sense and one small indel inducing a frameshift), each present in two families. Although each variant is currently classified as pathogenic and the cause of the diagnosed cardiomyopathy, the onset and/or clinical course differed in each patient. New genetic technology allows comprehensive yet cost-effective genetic analysis, although genetic interpretation, and clinical translation of identified variants should be carefully done in each family in a personalized manner.
Filiaciones:
Campuzano O:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Department of Biochemistry and Molecular Genetics, Hospital Clinic, Barcelona, Spain
Fernandez-Falgueras A:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Sarquella-Brugada G:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
César-Díaz S:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Arbelo E:
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
García-Álvarez A:
Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
Jordà P:
Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
Coll M:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Fiol JV:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Iglesias A:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Perez-Serra A:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Mates J:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Del Olmo B:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Ferrer C:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Alcalde M:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Puigmulé M:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Mademont-Soler I:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Pico F:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Lopez L:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Tiron C:
Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain
Brugada-Terradellas J:
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
Brugada R:
Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain
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