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SPG10 is a rare cause of spastic paraplegia in European families
  1. Rebecca Schüle (rebecca.schuele-freyer{at}uni-tuebingen.de)
  1. Hertie Institute for Clinical Brain Research and Center for Neurology, University of Tübingen, Germany
    1. Berry PH Kremer (h.kremer{at}neuro.umcn.nl)
    1. Department of Neurology, Radboud University Nijmegen Medical Centre, Netherlands
      1. Jan Kassubek (jan.kassubek{at}uni-ulm.de)
      1. Department of Neurology, University of Ulm, Germany
        1. Michaela Auer-Grumbach (michaela.auer-grumbach{at}klinikum-graz.at)
        1. Institute for Medical Research, University of Graz, Austria
          1. Vladimir S. Kostic (vkostic{at}sbb.co.yu)
          1. Department of Neurology, University of Belgrad, Serbia and Montenegro
            1. Thomas Klopstock (thomas.klopstock{at}med.uni-muenchen.de)
            1. Department of Neurology and Friedrich-Baur-Institute, Ludwig-Maximilians University Munich, Germany
              1. Sven Klimpe (klimpe{at}uni-mainz.de)
              1. Department of Neurology, University of Mainz, Germany
                1. Susanne Otto (s.otto{at}klinikum-bochum.de)
                1. Department of Neurology, Ruhr-University Bochum, Germany
                  1. Sylvia Bösch (sylvia.boesch{at}i-med.ac.at)
                  1. Department of Neurology, University of Innsbruck, Austria
                    1. Bart PC van de Warrenburg (b.vandewarrenburg{at}neuro.umcn.nl)
                    1. Department of Neurology, Radboud University Nijmegen Medical Centre, Netherlands
                      1. Ludger Schöls (ludger.schoels{at}uni-tuebingen.de)
                      1. Hertie Institute for Clinical Brain Research and Center for Neurology, University of Tübingen, Germany

                        Abstract

                        Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified so far.

                        Objective: To determine the frequency of SPG10 in European HSP families and to specify the SPG10 phenotype. Patients&Methods: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families.

                        Results: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory-motor neuropathy was detected by neurophysiology studies.

                        Conclusions: SPG10 accounts for about 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterized by spastic paraplegia with mostly subclinical peripheral neuropathy.

                        • KIF5A
                        • SPG10
                        • hereditary spastic paraplegia
                        • kinesin heavy chain

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