In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 628 ( 2022-01-19)
Abstract:
Most cases of inherited dilated cardiomyopathy (DCM) have no identified genetic cause. Here, Hakui and colleagues identified homozygous truncating mutations in the BAG5 gene, encoding the BAG co-chaperone 5 protein in five patients with inherited DCM. Heterozygous truncating mutations were also found in three patients with tachycardia-induced cardiomyopathy. Correction of a Bag5 mutant knock-in mouse model through gene therapy could ameliorate the DCM phenotype. BAG5 localized to junctional membrane complexes (JMCs), and mutant mouse cardiomyocytes under catecholamine stimulation demonstrated disrupted JMC architecture and calcium handling abnormalities. These findings suggest that BAG5 mutations can cause DCM, which, if diagnosed by genetic testing early enough, may be amenable to gene therapy.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abf3274
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022