Objective: To explore peripheral biomarkers related to Friedreich’s ataxia and identification of pathophysiological insights of complex phenotype

Background: Friedreich’s ataxia(FRDA) causes nervous system damage and movement problems which starts in children leading to early death. Although reduction in frataxin level is responsible for FRDA, other deregulated bio-markers may also contribute in disease phenotype mediated by cellular pathways.Therefore, identification of such biomarkers can be helpful in order to understand disease etiology and development of future medications. In the present study genome-wide expression analysis was performed in FRDA child patients as compared to normal children.

Methods: Transcriptome expression profiling of FRDA and controls peripheral blood cells was performed on a cohort of 28 patients and 10 controls that was extracted from GSE11204. To calculate mRNA expression, the bioconductor R package “limma” was used. Significantly deregulated genes were filtered using unpaired Student-t test and bonferrani test. The gene list associated with FRDA was extracted from DisGeNET database (http://www.disgenet.org). The ontology analysis of significantly altered genes was done using String Database (string-db.org).

Results: A total of 144 genes were found to be significantly altered (p<1.0E-06) in children manifest FRDA phenotype (Figure 1). Out of 144 genes, 76 genes were found to be downregulated and 68 genes were upregulated. It is also interesting to note that the identified genes were not reported earlier in FRDA provided at DisGeNET database. Genes associated with metabolic processes such as cellular metabolism of the transition metal, lipid metabolism etc (Table 1) were found to deregulated leading to altered metabolic processes damage and affect tissues leading to neuro-and cardio-degeneration.

Conclusions: The results suggest gene expression pattern consistent with metabolic process damage leading to neuro- and cardio-degeneration complexities in FRDA. Although the development of effective therapeutics enhanced analysis is required, identified biomarkers could also provide insight into pathway based etiology and may have predictive value in future clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/transcriptional-profiling-of-peripheral-blood-monocytes-from-child-friedreichs-ataxia-patient-new-molecules-and-patterns-of-gene-expression/