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EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement

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Abstract

Pontocerebellar hypoplasia (PCH) type 1 is characterized by the co-occurrence of spinal anterior horn involvement and hypoplasia of the cerebellum and pons. EXOSC3 has been recently defined as a major cause of PCH type 1. Three different phenotypes showing variable severity have been reported. We identified a homozygous mutation [c.395A > C/p.D132A] in EXOSC3 in four patients with muscle hypotonia, developmental delay, spinal anterior horn involvement, and prolonged survival, consistent with the “mild PCH1 phenotype”. Interestingly, isolated cerebellar hypoplasia limited to the hemispheres or involving both hemispheres and vermis was the main neuroradiologic finding, whereas the pontine volume was in the normal range for age. These findings strongly suggest that analysis of the EXOSC3 gene should be recommended also in patients with spinal anterior horn involvement and isolated cerebellar hypoplasia.

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Acknowledgments

We thank P. Broda for technical assistance. The patients samples were obtained from the “Cell Line and DNA Biobank from patients affected by genetic diseases” (G. Gaslini Institute)—Telethon Genetic Biobank Network (Project No. GTB12001).

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Neuroscience Department, Istituto G. Gaslini, Largo G. Gaslini 5, 16147, Genoa, Italy

    Roberta Biancheri, Francesca Pinto, Marisol Mirabelli-Badenier, Marina Pedemonte, Chiara Panicucci, Federico Zara, Pasquale Striano & Carlo Minetti

  2. Molecular Medicine Unit, IRCCS Stella Maris, Pisa, Italy

    Denise Cassandrini, Rosanna Trovato & Filippo Maria Santorelli

  3. Unit for Rare Disorders, Istituto G. Gaslini, Genoa, Italy

    Maja Di Rocco

  4. Cologne Center for Genomics, University of Cologne, Cologne, Germany

    Holger Trucks & Thomas Sander

  5. Pediatric Neuroradiology Unit, Istituto G. Gaslini, Genoa, Italy

    Andrea Rossi

  6. Pediatric Neurology and Muscular Diseases Unit, University of Genova and G. Gaslini Institute, Genoa, Italy

    Pasquale Striano & Carlo Minetti

Authors
  1. Roberta Biancheri
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  2. Denise Cassandrini
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  3. Francesca Pinto
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  4. Rosanna Trovato
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  5. Maja Di Rocco
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  6. Marisol Mirabelli-Badenier
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  7. Marina Pedemonte
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  8. Chiara Panicucci
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  9. Holger Trucks
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  10. Thomas Sander
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  11. Federico Zara
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  12. Andrea Rossi
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  13. Pasquale Striano
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  14. Carlo Minetti
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  15. Filippo Maria Santorelli
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Corresponding author

Correspondence to Roberta Biancheri.

Additional information

Carlo Minetti and Filippo Maria Santorelli contributed equally to this work.

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Biancheri, R., Cassandrini, D., Pinto, F. et al. EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. J Neurol 260, 1866–1870 (2013). https://doi.org/10.1007/s00415-013-6896-0

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  • DOI: https://doi.org/10.1007/s00415-013-6896-0

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