2026-05-08T20:04:29Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/251362025-12-18T12:56:18Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Ochoa, Juan Pablo author Espinosa, Maria Ángeles author Gayan-Ordas, Jara author Fernández-Valledor, Andrea author Gallego-Delgado, María author Tirón, Coloma author Lozano-Ibañez, Adrián author García-Pinilla, José Manuel author Rodríguez-Palomares, José F author Larrañaga-Moreira, José María author Llamas-Gómez, Helena author Ripoll-Vera, Tomas author Braza-Boïls, Aitana author Vilches, Silvia author Méndez, Irene author Bascompte-Claret, Ramón author García-Álvarez, Ana author Villacorta, Eduardo author Fernandez-Lozano, Ignacio author Lara-Pezzi, Enrique author Garcia-Pavia, Pablo author 2024-06-18 Background: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. Objectives: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. Methods: We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). Results: Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). Conclusions: Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated. JACC Clin Electrophysiol. 2024 Jun 18:S2405-500X(24)00367-0. 2405-5018 JACC-CLINICAL ELECTROPHYSIOLOGY 39001760 https://hdl.handle.net/20.500.12105/25136 cardiac conduction disorders cardiomyopathy genetics pacemaker sudden cardiac death Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation.