RT Journal Article
T1 Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations.
A1 Dominguez, Fernando
A1 Cuenca, Sofia
A1 Bilinska, Zofia
A1 Toro, Rocio
A1 Villard, Eric
A1 Barriales-Villa, Roberto
A1 Ochoa, Juan Pablo
A1 Asselbergs, Folkert
A1 Sammani, Arjan
A1 Franaszczyk, Maria
A1 Akhtar, Mohammed
A1 Coronado-Albi, Maria Jose
A1 Rangel-Sousa, Diego
A1 Rodriguez-Palomares, Jose F
A1 Jimenez-Jaimez, Juan
A1 Garcia-Pinilla, Jose Manuel
A1 Ripoll-Vera, Tomas
A1 Mogollon-Jimenez, Maria Victoria
A1 Fontalba-Romero, Ana
A1 Garcia-Medina, Dolores
A1 Palomino-Doza, Julian
A1 de Gonzalo-Calvo, David
A1 Cicerchia, Marcos
A1 Salazar-Mendiguchia, Joel
A1 Salas, Clara
A1 Pankuweit, Sabine
A1 Hey, Thomas Morris
A1 Mogensen, Jens
A1 Barton, Paul J
A1 Charron, Philippe
A1 Elliott, Perry
A1 Garcia-Pavia, Pablo
K1 BAG3
K1 Dilated cardiomyopathy
K1 Genetics
K1 Prognosis
AB The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations.
PB Elsevier
YR 2018
FD 2018-08-13
LK http://hdl.handle.net/10668/13194
UL http://hdl.handle.net/10668/13194
LA en
NO Domínguez F, Cuenca S, Bilińska Z, Toro R, Villard E, Barriales-Villa R, et al. Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations. J Am Coll Cardiol. 2018 Nov 13;72(20):2471-2481
DS RISalud
RD Apr 6, 2025