Rare Genetic Variants in Young Adults Requiring Pacemaker Implantation.

Fecha de publicación: 18/06/2024 Fecha Ahead of Print: 10/07/2024

Autores de IIS La Fe

Aitana Braza Boils

Autor

Participantes ajenos a IIS La Fe

Ochoa, Juan Pablo
Espinosa, Maria Angeles
Gayan-Ordas, Jara
Fernandez-Valledor, Andrea
Gallego-Delgado, Maria
Tiron, Coloma
Lozano-Ibanez, Adrian
Garcia-Pinilla, Jose Manuel
Rodriguez-Palomares, Jose F
Larranaga-Moreira, Jose Maria
Llamas-Gomez, Helena
Ripoll-Vera, Tomas
Vilches, Silvia
Mendez, Irene
Bascompte-Claret, Ramon
Garcia-Alvarez, Ana
Villacorta, Eduardo
Fernandez-Lozano, Ignacio
Lara-Pezzi, Enrique
Garcia-Pavia, Pablo

Grupos

Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

Investigador Principal

Aitana Braza Boils

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 2405-500X, 2405-5018
Tipo:: Article
Páginas:: 2250-2260
DOI:: 10.1016/j.jacep.2024.05.008
Factor de Impacto:: 2,115 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Keywords

cardiac conduction disorders; cardiomyopathy; genetics; pacemaker; sudden cardiac death

Campos de estudio

Proyectos asociados

RED INVESTIGACION (RECAVA)

RD06/0014/0004 . INSTITUTO DE SALUD CARLOS III; FUNDACION PARA LA INV BIOMEDICA- HOSPITAL GREGORIO MARAÑON; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006