Frontiers in Genetics (May 2019)
Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies
- Oscar Campuzano,
- Oscar Campuzano,
- Oscar Campuzano,
- Oscar Campuzano,
- Anna Fernandez-Falgueras,
- Georgia Sarquella-Brugada,
- Georgia Sarquella-Brugada,
- Sergi Cesar,
- Elena Arbelo,
- Elena Arbelo,
- Ana García-Álvarez,
- Paloma Jordà,
- Monica Coll,
- Victoria Fiol,
- Anna Iglesias,
- Anna Iglesias,
- Alexandra Perez-Serra,
- Alexandra Perez-Serra,
- Jesus Mates,
- Bernat del Olmo,
- Carles Ferrer,
- Mireia Alcalde,
- Mireia Alcalde,
- Marta Puigmulé,
- Irene Mademont-Soler,
- Ferran Pico,
- Laura Lopez,
- Coloma Tiron,
- Josep Brugada,
- Josep Brugada,
- Josep Brugada,
- Ramon Brugada,
- Ramon Brugada,
- Ramon Brugada,
- Ramon Brugada
Affiliations
- Oscar Campuzano
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Oscar Campuzano
- Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
- Oscar Campuzano
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Oscar Campuzano
- Department of Biochemistry and Molecular Genetics, Hospital Clinic, Barcelona, Spain
- Anna Fernandez-Falgueras
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Georgia Sarquella-Brugada
- Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
- Georgia Sarquella-Brugada
- Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
- Sergi Cesar
- Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
- Elena Arbelo
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Elena Arbelo
- Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Ana García-Álvarez
- Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Paloma Jordà
- Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Monica Coll
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Victoria Fiol
- Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
- Anna Iglesias
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Anna Iglesias
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Alexandra Perez-Serra
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Alexandra Perez-Serra
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Jesus Mates
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Bernat del Olmo
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Carles Ferrer
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Mireia Alcalde
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Mireia Alcalde
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Marta Puigmulé
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Irene Mademont-Soler
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Ferran Pico
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Laura Lopez
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Coloma Tiron
- Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain
- Josep Brugada
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Josep Brugada
- Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
- Josep Brugada
- Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
- Ramon Brugada
- Cardiovascular Genetics Center, Biomedical Research Institute of Girona, University of Girona, Girona, Spain
- Ramon Brugada
- Department of Medical Science, School of Medicine, University of Girona, Girona, Spain
- Ramon Brugada
- Centro Investigación Biomédica Red Enfermedades Cardiovasculares, Madrid, Spain
- Ramon Brugada
- Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain
- DOI
- https://doi.org/10.3389/fgene.2019.00450
- Journal volume & issue
-
Vol. 10
Abstract
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.
Keywords
