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Article

Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters

by
Sara Petrillo
1,
Alessia Perna
2,
Andrea Quatrana
1,
Gabriella Silvestri
3,4,
Enrico Bertini
1,
Fiorella Piemonte
1,* and
Massimo Santoro
5
1
Unit of Muscular and Neurodegenerative Diseases, Children’s Hospital Bambino Gesù, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00146 Rome, Italy
2
Center for Neuromuscular and Neurological Rare Diseases, San Camillo Forlanini Hospital, 00152 Rome, Italy
3
Department of Neurosciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
4
UOC of Neurology, Area of Neuroscience, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
5
Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(21), 11615; https://doi.org/10.3390/ijms252111615
Submission received: 13 September 2024 / Revised: 11 October 2024 / Accepted: 24 October 2024 / Published: 29 October 2024
(This article belongs to the Collection Feature Papers in Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Friedreich ataxia (FRDA) is the most common inherited ataxia, primarily impacting the nervous system and the heart. It is characterized by GAA repeat expansion in the FXN gene, leading to reduced mitochondrial frataxin levels. Previously, we described a family displaying two expanded GAA alleles, not only in the proband affected by late-onset FRDA but also in the younger asymptomatic sister. The molecular characterization of the expanded repeats showed that the affected sister carried two canonical uninterrupted GAA expended repeats, whereas the asymptomatic sister had a compound heterozygous for a canonical GAA repeat and an expanded GAAGGA motif. Therefore, we decided to perform RNA sequencing (RNA-seq) on fibroblasts from both sisters in order to understand whether some genes and/or pathways might be differently involved in the occurrence of FRDA clinical manifestation. The transcriptomic analysis revealed 398 differentially expressed genes. Notably, TLR4, IL20RB, and SLITRK5 were up-regulated, while TCF21 and GRIN2A were down-regulated, as validated by qRT-PCR. Gene ontology (GO) enrichment and network analysis highlighted significant involvement in immune response and neuronal functions. Our results, in particular, suggest that TLR4 may contribute to inflammation in FRDA, while IL20RB, SLITRK5, TCF21, and GRIN2A dysregulation may play roles in the disease pathogenesis. This study introduces new perspectives on the inflammatory and developmental aspects in FRDA, offering potential targets for therapeutic intervention.
Keywords: Friedreich’s ataxia; RNA-seq; transcriptomic analysis; TLR4; inflammation; neurodegenerative disease; differentially expressed genes (DEGs) Friedreich’s ataxia; RNA-seq; transcriptomic analysis; TLR4; inflammation; neurodegenerative disease; differentially expressed genes (DEGs)

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MDPI and ACS Style

Petrillo, S.; Perna, A.; Quatrana, A.; Silvestri, G.; Bertini, E.; Piemonte, F.; Santoro, M. Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters. Int. J. Mol. Sci. 2024, 25, 11615. https://doi.org/10.3390/ijms252111615

AMA Style

Petrillo S, Perna A, Quatrana A, Silvestri G, Bertini E, Piemonte F, Santoro M. Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters. International Journal of Molecular Sciences. 2024; 25(21):11615. https://doi.org/10.3390/ijms252111615

Chicago/Turabian Style

Petrillo, Sara, Alessia Perna, Andrea Quatrana, Gabriella Silvestri, Enrico Bertini, Fiorella Piemonte, and Massimo Santoro. 2024. "Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters" International Journal of Molecular Sciences 25, no. 21: 11615. https://doi.org/10.3390/ijms252111615

APA Style

Petrillo, S., Perna, A., Quatrana, A., Silvestri, G., Bertini, E., Piemonte, F., & Santoro, M. (2024). Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters. International Journal of Molecular Sciences, 25(21), 11615. https://doi.org/10.3390/ijms252111615

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