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Consolidating the Role of TDP2 Mutations in Recessive Spinocerebellar Ataxia Associated with Pediatric Onset Drug Resistant Epilepsy and Intellectual Disability (SCAR23)

  • Claudia CiaccioEmail author
  • Raffaele Castello
  • Silvia Esposito
  • Michele Pinelli
  • Vincenzo Nigro
  • Giorgio Casari
  • Luisa Chiapparini
  • Chiara Pantaleoni
  • TUDP Study Group
  • Stefano D’Arrigo
Short reports
  • 32 Downloads

Abstract

Spinocerebellar Ataxia 23 (SCAR23) is a newly described condition caused by mutations in TDP2 gene. To date, only four patients from two families have been reported, all carrying the same homozygous mutation. We describe a fifth patient, carrying a novel mutation in the same gene, thus confirming the role of TDP2 mutations in determining the disease and defining the main features SCAR23: pediatric onset ataxia and drug-resistant epilepsy and intellectual disability. We further show the clinical presentation which is associated with the neuroradiological evidence of progressive cerebellar atrophy, giving the evidence that SCAR23 can be classified as a degenerative condition.

Keywords

Pediatric ataxia Spinocerebellar ataxia SCAR23 TDP2 Cerebellar atrophy 

Notes

Acknowledgements

The authors thank the patient and her family for the cooperation during the diagnostic process.

Paper Collaborators: TUDP Members:

Annalaura Torella (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy; Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy), Gerarda Cappuccio (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy, Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy), Francesco Musacchia (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy), Margherita Mutarelli (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy), Diego Carrella (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy), Giuseppina Vitiello (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy; Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy; Department of Pediatrics, ASST Lariana Sant’Anna Hospital, San Fermo della Battaglia, Como, Italy), Giancarlo Parenti (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy; Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy), Valeria Capra (Neuroscience Department, Giannina Gaslini Institute, Genoa, Italy), Vincenzo Leuzzi (Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy), Angelo Selicorni (Department of Pediatrics, ASST Lariana Sant’Anna Hospital, San Fermo della Battaglia, Como, Italy), Silvia Maitz (Fondazione MBBM; Monza, Italy), Nicola Brunetti-Pierri (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy; Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy), Sandro Banfi (Telethon Institute of Genetics and Medicine, Pozzuoli, Naples, Italy; Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy), Marcella Zollino (Institute of Genomic Medicine, Catholic University, Gemelli Hospital Foundation, Rome, Italy), Martino Montomoli (Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience 10. Department, A Meyer Children’s Hospital, University of Florence, Florence, Italy), Donatella Milani (Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy), Corrado Romano (Oasi Research Institute - IRCCS, Troina, Italy), Albina Tummolo (Department of Metabolic Diseases, Clinical Genetics and Diabetology, Giovanni XXIII Children’s Hospital, Bari, Italy), Daniele De Brasi (Department of Pediatrics, AORN Santobono Pausilipon, Naples, Italy), Antonietta Coppola (Department of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Center, Federico II, University of Naples, Naples, Italy), Claudia Santoro (Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy).

Funding

This study was founded by Telethon Foundation (GSP15001).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

An informed consent was obtained from the patient’s parents for data and pictures publication.

References

  1. 1.
    Gómez-Herreros F, Schuurs-Hoeijmakers JH, McCormack M, Greally MT, Rulten S, Romero-Granados R, et al. TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. Nat Genet. 2014;46(5):516–21.CrossRefGoogle Scholar
  2. 2.
    Zagnoli-Vieira G, Bruni F, Thompson K, He L, Walker S, de Brouwer APM, et al. Confirming TDP2 mutation in spinocerebellar ataxia autosomal recessive 23 (SCAR23). Neurol Genet. 2018;4(4):e262.CrossRefGoogle Scholar
  3. 3.
    Gómez-Herreros F, Romero-Granados R, Zeng Z, Alvarez-Quilón A, Quintero C, Ju L, et al. TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genet. 2013;9(3):e1003226.CrossRefGoogle Scholar
  4. 4.
    Musacchia F, Ciolfi A, Mutarelli M, Bruselles A, Castello R, Pinelli M, et al. VarGenius executes cohort-level DNA-seq variant calling and annotation and allows to manage the resulting data through a PostgreSQL database. BMC Bioinformatics. 2018;19(1):477.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Claudia Ciaccio
    • 1
    Email author
  • Raffaele Castello
    • 2
  • Silvia Esposito
    • 1
  • Michele Pinelli
    • 2
    • 3
  • Vincenzo Nigro
    • 2
    • 4
  • Giorgio Casari
    • 2
    • 5
  • Luisa Chiapparini
    • 6
  • Chiara Pantaleoni
    • 1
  • TUDP Study Group
  • Stefano D’Arrigo
    • 1
  1. 1.Developmental Neurology UnitFondazione IRCCS Istituto Neurologico Carlo BestaMilanItaly
  2. 2.Telethon Institute of Genetics and MedicineNaplesItaly
  3. 3.Department of Translational Medicine, Section of PediatricsFederico II UniversityNaplesItaly
  4. 4.Department of Precision MedicineUniversity of Campania “Luigi Vanvitelli”NaplesItaly
  5. 5.Vita-Salute San Raffaele UniversityMilanItaly
  6. 6.Neuroradiology DepartmentFondazione IRCCS Istituto Neurologico Carlo BestaMilanItaly

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