ArticleScientific reports2026
Validation of circulating miR-323a-3p and miR-625-3p to classify hypertrophic cardiomyopathy in Friedreich's ataxia.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Friedreich's ataxia (FRDA) is an inherited neurodegenerative disorder frequently complicated by hypertrophic cardiomyopathy (HCM), a major cause of morbidity and mortality in these patients. Conventional protein biomarkers, such as high-sensitivity troponin or collagen turnover markers, provide only modest diagnostic accuracy, highlighting the need for more sensitive tools. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers, but independent validation in FRDA remains limited. We analyzed a cohort of FRDA patients (n = 34) and age-, sex-, and race-matched healthy controls (n = 34). Expression of a previously proposed miRNA signature was evaluated in plasma using RT-qPCR, with normalization to miR-16-5p, replicating prior methodology. Echocardiographic parameters were compared across subgroups. Associations between differential miRNA expression, comorbidities (diabetes mellitus, cardiomyopathy), and echocardiographic measures were evaluated. Receiver Operating Characteristic (ROC) curves and multivariable logistic regression assessed diagnostic performance. Five of seven candidate miRNAs were validated as differentially expressed in FRDA compared with controls. Among patients, miR-128-3p, miR-130b-5p, miR-151a-5p, miR-330-3p, and miR-142-3p were significantly up-regulated in those with diabetes. For cardiomyopathy, both miR-323a-3p (previously described by our group) and miR-625-3p showed strong associations. A multivariable model combining miR-323a-3p and miR-625-3p achieved promising discriminative performance for HCM (Area Under the Curve (AUC) = 0.84; sensitivity 80%; specificity 71.4%), outperforming traditional protein biomarkers. This two-miRNA panel offers robust non-invasive prediction of HCM in FRDA and highlights metabolic miRNAs as dual biomarkers for diabetes comorbidity. Prospective longitudinal studies and development of standardized diagnostic kits are warranted to integrate miRNA profiling into FRDA clinical care.
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