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).
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The authors declare that they have no conflicts of interest.
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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