Publication:
Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy.

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2020-01-21

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Belmonte, Thalia
Mangas, Alipio
Calderon-Dominguez, Maria
Quezada-Feijoo, Maribel
Ramos, Monica
Campuzano, Oscar
Gomez, Silvia
Peña, Maria Luisa
Cubillos-Arango, Andres M
Dominguez, Fernando

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Elsevier
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Etiology-based diagnosis of dilated cardiomyopathy (DCM) is challenging. We evaluated whether peripheral microRNAs (miRNAs) could be used to characterize the DCM etiology. We investigated the miRNA plasma profiles of 254 subjects that comprised 5 groups: Healthy subjects (n = 70), idiopathic DCM patients (n = 55), ischemic DCM patients (n = 60) and 2 groups of patients with pathogenic variants responsible for familial DCM in the LMNA (LMNAMUT, n = 37) and BAG3 (BAG3MUT, n = 32) genes. Diagnostic performance was assessed using receiver operating characteristic curves. In a screening study (n = 30), 179 miRNAs robustly detected in plasma samples were profiled in idiopathic DCM and carriers of pathogenic variants. After filtering, 26 miRNA candidates were selected for subsequent quantification in the whole study population. In the validation study, a 6-miRNA panel identified familial DCM with an AUC (95% confidence interval [CI]) of 87.8 (82.0-93.6). The 6-miRNA panel also distinguished between specific DCM etiologies with AUCs ranging from 85.9 to 89.9. Only 1 to 10 of the subjects in the first and second tertiles of the 6-miRNA panel were patients with familial DCM. Additionally, a 5-miRNA panel showed an AUC (95% CI) of 87.5 (80.4-94.6) for the identification of carriers with pathogenic variants who were phenotypically negative for DCM. The 5-miRNA panel discriminated between carriers and healthy controls with AUCs ranging from 83.2 to 90.8. Again, only 1 to 10 of the subjects in the lowest tertiles of the 5-miRNA panel were carriers of pathogenic variants. In conclusion, miRNA signatures could be used to rule out patients with pathogenic variants responsible for DCM.

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Adult
Aged
Biomarkers
Cardiomyopathy, Dilated
Case-Control Studies
Heterozygote
Humans
MicroRNAs
Middle Aged
Reproducibility of Results

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Biomarcadores
Cardiomiopatia dilatada
Estudios de casos y controles
Heterocigoto
MicroARNs
Reproducibilidad de los resultados
Persona de mediana edad

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Citation

Belmonte T, Mangas A, Calderon-Dominguez M, Quezada-Feijoo M, Ramos M, Campuzano O, et al. Peripheral microRNA panels to guide the diagnosis of familial cardiomyopathy. Transl Res. 2020 Apr;218:1-15