Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients

Abstract

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia characterized by a combination of neurological involvement, cardiomyopathy, and skeletal and glucose metabolism disturbances. FRDA is caused by mutations in FXN gene that results in reduction of mRNA and protein levels of frataxin. Previous microarray and real-time quantitative PCR (qPCR) studies showed that the downregulation of FXN is associated with a complex gene expression profile. However, these studies showed a wide variability in the subset of genes with altered expression among tissues and models. Genes differentially expressed in peripheral blood cells (PBC) could potentially help in the understanding of FRDA pathophysiology and also function as reliable disease biomarkers obtained from an easily accessible tissue, which could have implications in clinical practice. This study aimed to validate by qPCR the expression of 26 genes, revealed as differentially expressed by other studies, using peripheral blood cells (PBC) of 11 FRDA patients compared to 11 healthy controls. We found a robust downregulation of FXN, but no statistically significant differences were found between FRDA and controls for the remaining genes. Except for FXN, our study did not find a differential gene expression profile in PBC of FRDA patients and a reliable gene expression profile biomarker in a clinical relevant and noninvasive tissue remains unclear.

Epigenetic regulation of clinical manifestations of Friedreich's disease

“…Тем не менее длина экспансии может объяснить лишь 50% вариабельности фенотипа, что свидетельствует о наличии других факторов, определяющих клиническую картину заболевания. Обсуждается роль генов-модификаторов, стабилизирующих гексануклеотидных GAGGAA-вставок, соматического мозаицизма, нестабильности экспансии в течение жизни, однако в последние годы все большее значение придается эпигенетическим механизмам, осуществляющим регуляцию экспрессии генов без изменений нуклеотидной последовательности ДНК [17].…”