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Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations.

Abstract：

BACKGROUND: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. OBJECTIVES:This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Domínguez F,Cuenca S,Bilińska Z,Toro R,Villard E,Barriales-Villa R,Ochoa JP,Asselbergs F,Sammani A,Franaszczyk M,Akhtar M,Coronado-Albi MJ,Rangel-Sousa D,Rodriguez-Palomares JF,Jiménez-Jáimez J,Garcia-Pinilla JM,Ripoll-Ve

doi

10.1016/j.jacc.2018.08.2181

subject

Has Abstract

pub_date

2018-11-13 00:00:00

pages

2471-2481

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(18)38517-6

journal_volume

pub_type

杂志文章,多中心研究

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Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations.