Biomedicines (Jul 2022)
miRNAs and isomiRs: Serum-Based Biomarkers for the Development of Intellectual Disability and Autism Spectrum Disorder in Tuberous Sclerosis Complex
- Mirte Scheper,
- Alessia Romagnolo,
- Zein Mersini Besharat,
- Anand M. Iyer,
- Romina Moavero,
- Christoph Hertzberg,
- Bernhard Weschke,
- Kate Riney,
- Martha Feucht,
- Theresa Scholl,
- Borivoj Petrak,
- Alice Maulisova,
- Rima Nabbout,
- Anna C. Jansen,
- Floor E. Jansen,
- Lieven Lagae,
- Malgorzata Urbanska,
- Elisabetta Ferretti,
- Aleksandra Tempes,
- Magdalena Blazejczyk,
- Jacek Jaworski,
- David J. Kwiatkowski,
- Sergiusz Jozwiak,
- Katarzyna Kotulska,
- Krzysztof Sadowski,
- Julita Borkowska,
- Paolo Curatolo,
- James D. Mills,
- Eleonora Aronica,
- EPISTOP Consortium Members
Affiliations
- Mirte Scheper
- Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Alessia Romagnolo
- Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Zein Mersini Besharat
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
- Anand M. Iyer
- Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Romina Moavero
- Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, 00133 Rome, Italy
- Christoph Hertzberg
- Diagnose-und Behandlungszentrum für Kinder, Vivantes-Klinikum Neukölln, 12351 Berlin, Germany
- Bernhard Weschke
- Department of Neuropediatrics, Charité University Medicine Berlin, 13353 Berlin, Germany
- Kate Riney
- Faculty of Medicine, The University of Queensland, Herston, QLD 4029, Australia
- Martha Feucht
- Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, “Member of ERN EpiCARE”, 1090 Vienna, Austria
- Theresa Scholl
- Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, “Member of ERN EpiCARE”, 1090 Vienna, Austria
- Borivoj Petrak
- Motol University Hospital, Charles University, 15000 Prague, Czech Republic
- Alice Maulisova
- Motol University Hospital, Charles University, 15000 Prague, Czech Republic
- Rima Nabbout
- Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades University Hospital, APHP, Member of ERN EpiCARE, Université de Paris, 149 Rue de Sèvres, 75015 Paris, France
- Anna C. Jansen
- Department of Translational Neurosciences, University of Antwerp, 2000 Antwerp, Belgium
- Floor E. Jansen
- Department of Child Neurology, Brain Center University Medical Center, Member of ERN EpiCare, 3584 BA Utrecht, The Netherlands
- Lieven Lagae
- Department of Development and Regeneration Section Pediatric Neurology, University Hospitals KU Leuven, 3000 Leuven, Belgium
- Malgorzata Urbanska
- Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
- Elisabetta Ferretti
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
- Aleksandra Tempes
- International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland
- Magdalena Blazejczyk
- International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland
- Jacek Jaworski
- International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland
- David J. Kwiatkowski
- Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Sergiusz Jozwiak
- Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
- Katarzyna Kotulska
- Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
- Krzysztof Sadowski
- Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
- Julita Borkowska
- Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland
- Paolo Curatolo
- Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, 00133 Rome, Italy
- James D. Mills
- Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- Eleonora Aronica
- Department of (Neuro)Pathology Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
- EPISTOP Consortium Members
- DOI
- https://doi.org/10.3390/biomedicines10081838
- Journal volume & issue
-
Vol. 10,
no. 8
p. 1838
Abstract
Tuberous sclerosis complex (TSC) is a rare multi-system genetic disorder characterized by a high incidence of epilepsy and neuropsychiatric manifestations known as tuberous-sclerosis-associated neuropsychiatric disorders (TANDs), including autism spectrum disorder (ASD) and intellectual disability (ID). MicroRNAs (miRNAs) are small regulatory non-coding RNAs that regulate the expression of more than 60% of all protein-coding genes in humans and have been reported to be dysregulated in several diseases, including TSC. In the current study, RNA sequencing analysis was performed to define the miRNA and isoform (isomiR) expression patterns in serum. A Receiver Operating Characteristic (ROC) curve analysis was used to identify circulating molecular biomarkers, miRNAs, and isomiRs, able to discriminate the development of neuropsychiatric comorbidity, either ASD, ID, or ASD + ID, in patients with TSC. Part of our bioinformatics predictions was verified with RT-qPCR performed on RNA isolated from patients’ serum. Our results support the notion that circulating miRNAs and isomiRs have the potential to aid standard clinical testing in the early risk assessment of ASD and ID development in TSC patients.
Keywords
- epilepsy
- tuberous sclerosis complex
- biomarkers
- serum
- autism spectrum disorder
- intellectual disability
