Interpreting the actionable clinical role of rare variants associated with short QT syndrome.

Autor:	Martínez-Barrios E; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain.; Medical Science Department, School of Medicine, Universitat de Girona, C/ Emili Grahit 77, Girona, Catalonia, 17003, Spain., Greco A; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Cruzalegui J; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Cesar S; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Díez-Escuté N; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Cerralbo P; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Chipa F; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Zschaeck I; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Slanovic L; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain., Mangas A; Medicine Department, School of Medicine, University of Cádiz, Cádiz, 11002, Spain.; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cádiz, 11009, Spain.; Internal Medicine Department, Puerta del Mar University Hospital, Cádiz, 11009, Spain., Toro R; Medicine Department, School of Medicine, University of Cádiz, Cádiz, 11002, Spain.; Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cádiz, 11009, Spain., Brugada J; Arrhythmias Unit, Hospital Clinic, University of Barcelona, Barcelona, 08036, Spain.; Centro Investigación Biomédica en Red-Cardiovascular (CIBERCV), Madrid, 28029, Spain., Sarquella-Brugada G; Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950, Spain. georgia@brugada.org.; Arrítmies Pediàtriques, Cardiologia Genètica i Mort Sobtada, Malalties Cardiovasculars en el Desenvolupament, Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, 08950, Spain. georgia@brugada.org.; Medical Science Department, School of Medicine, Universitat de Girona, C/ Emili Grahit 77, Girona, Catalonia, 17003, Spain. georgia@brugada.org.; Pediatrics Department, School of Medicine, Universitat de Barcelona, Barcelona, 08036, Spain. georgia@brugada.org., Campuzano O; Medical Science Department, School of Medicine, Universitat de Girona, C/ Emili Grahit 77, Girona, Catalonia, 17003, Spain. oscar@brugada.org.; Centro Investigación Biomédica en Red-Cardiovascular (CIBERCV), Madrid, 28029, Spain. oscar@brugada.org.; Institut d'Investigació Biomèdiques de Girona (IDIBGI-CERCA), Salt, 17190, Spain. oscar@brugada.org.
Jazyk:	angličtina
Zdroj:	Human genetics [Hum Genet] 2024 Dec; Vol. 143 (12), pp. 1499-1508. Date of Electronic Publication: 2024 Nov 06.
DOI:	10.1007/s00439-024-02713-x
Abstrakt:	Genetic testing is recommended in the diagnosis of short QT syndrome. This rare inherited lethal entity is characterized by structural normal hearts with short QT intervals in the electrocardiogram. Few families diagnosed with this arrhythmogenic disease have been reported worldwide so far, impeding a comprehensive understanding of this syndrome. Unraveling the origin of the disease helps to the early identification of genetic carriers at risk. However, only rare variants with a definite deleterious role should be actionable in clinical practice. Our aim was to perform a comprehensive update and reinterpretation, according to the American College of Medical Genetics and Genomics recommendations of all rare variants currently associated with short QT syndrome. We identified 34 rare variants. Reanalysis showed that only nine variants played a deleterious role associated with a definite short QT syndrome phenotype. These variants were located in the four main genes: KCNQ1, KCNH2, KCNJ2 or SLC4A3. Additional rare variants located in other genes were associated with other conditions with phenotypic shortened QT intervals, but not definite diagnosis of short QT syndrome. Periodically updating of rare variants, especially those previously classified as unknown, helps to clarify the role of rare variants and translate genetic data into clinical practice. Competing Interests: Declarations Ethical approval Not necessary. Consent to participate Not necessary. Competing interests The authors declare no competing interests. (© 2024. The Author(s).)
Databáze:	MEDLINE
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