Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants
Por:
Campuzano O, Fernandez-Falgueras A, Lemus X, Sarquella-Brugada G, César-Díaz S, Coll M, Mates J, Arbelo E, Jordà P, Perez-Serra A, Del Olmo B, Ferrer-Costa C, Iglesias A, Fiol JV, Puigmulé M, Lopez L, Pico F, Brugada-Terradellas J and Brugada R
Publicada:
1 jul 2019
Ahead of Print:
16 jul 2019
Categoría:
Medicine (miscellaneous)
Resumen:
Short QT syndrome, one of the most lethal entities associated with sudden cardiac death, is a rare genetic disease characterized by short QT intervals detected by electrocardiogram. Several genetic variants are causally linked to the disease, but there has yet to be a comprehensive analysis of variants among patients with short QT syndrome. To fill this gap, we performed an exhaustive study of variants currently catalogued as deleterious in short QT syndrome according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Analysis of the 32 variants described in the literature determined that only nine (28.12%) have a conclusive pathogenic role. All definitively pathogenic variants are located in KCNQ1, KCNH2, or KCNJ2; three genes encoding potassium channels. Other variants located in genes encoding calcium or sodium channels are associated with electrical alterations concomitant with shortened QT intervals but do not guarantee a diagnosis of short QT syndrome. We recommend caution regarding previously reported variants classified as pathogenic. An exhaustive re-analysis is necessary to clarify the role of each variant before routinely translating genetic findings to the clinical setting.
Filiaciones:
Campuzano O:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain.
Centro Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain.
Medical Science Department, School of Medicine, University of Girona, 17071 Girona, Spain.
Biochemistry and Molecular Genetics Department, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain.
Fernandez-Falgueras A:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Lemus X:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Sarquella-Brugada G:
Medical Science Department, School of Medicine, University of Girona, 17071 Girona, Spain
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain
César-Díaz S:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain
Coll M:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Mates J:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Arbelo E:
Centro Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Jordà P:
Centro Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Perez-Serra A:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Del Olmo B:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Ferrer-Costa C:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Iglesias A:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Fiol JV:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain
Puigmulé M:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Lopez L:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Pico F:
Cardiovascular Genetics Center, University of Girona-IDIBGI, 17190 Girona, Spain
Brugada-Terradellas J:
Centro Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, 08950 Barcelona, Spain
Arrhythmias Unit, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
Brugada R:
Cardiology Service, Hospital Josep Trueta, University of Girona, 17007 Girona, Spain.
Green Submitted, Green Accepted, gold
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