Abstract
SPAST mutations are the most common cause of autosomal dominant hereditary spastic paraplegias (AD-HSPs), but many spastic paraplegia patients are found to carry no mutations in this gene. In order to assess the contribution of ATL1 and REEP1 in AD-HSP, we performed mutational analysis in 27 SPAST-negative AD-HSP families. We found three novel ATL1 mutations and one REEP1 mutation in five index-patients. In 110 patients with sporadic adult-onset upper motor neuron syndromes, a novel REEP1 mutation was identified in one patient. Apart from a significantly younger age at onset in ATL1 patients and restless legs in some, the clinical phenotype of ATL1 and REEP1 was similar to other pure AD-HSPs.
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Acknowledgments
We would like to thank all the patients and their families.
Conflicts of interest
SdB, SV, AM, FB and EJK report no disclosures. JV and LvdB: This work was supported by the VSB Fonds, The Thierry Latran Foundation, Prinses Beatrix Fonds, Catharijne Stichting, H. Kersten and M. Kersten, J. R. van Dijk, the Adessium Foundation, and the research leading to these results has received funding from the European Community’s Health Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 259867 HS receives or has received research support from the European Union and the Netherlands Organisation for Health Research and Development (ZONMW). BK receives or has received research support from the University Medical Centre Groningen, and the BCN-Brain Research Institute. BvdW receives or has received research support from the Prinses Beatrix Fonds, the European Union, the Brain Foundation, Ipsen Pharmaceuticals, the Gossweiler Foundation, and the Royal Dutch Society for Physical Therapy.
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This study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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de Bot, S.T., Veldink, J.H., Vermeer, S. et al. ATL1 and REEP1 mutations in hereditary and sporadic upper motor neuron syndromes. J Neurol 260, 869–875 (2013). https://doi.org/10.1007/s00415-012-6723-z
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DOI: https://doi.org/10.1007/s00415-012-6723-z