SPG10 is a rare cause of spastic paraplegia in European families
- R Schüle1,
- B P H Kremer2,
- J Kassubek3,
- M Auer-Grumbach4,
- V Kostic5,
- T Klopstock6,
- S Klimpe7,
- S Otto8,
- S Boesch9,
- B P van de Warrenburg2,
- L Schöls1
- 1Hertie-Institute for Clinical Brain Research and Department of Neurology, Eberhard Karls-University Tübingen, Germany
- 2Department of Neurology, Radboud University Nijmegen Medical Centre, The Netherlands
- 3Department of Neurology, University of Ulm, Germany
- 4Institute for Medical Research, University of Graz, Austria
- 5Department of Neurology, University of Belgrad, Serbia
- 6Department of Neurology and Friedrich-Baur-Institute, Ludwig-Maximilians University Munich, Germany
- 7Department of Neurology, University of Mainz, Germany
- 8Department of Neurology, Ruhr-University Bochum, Germany
- 9Department of Neurology, University of Innsbruck, Austria
- Dr L Schöls, Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str 3, D–72076 Tübingen, Germany; Ludger.Schoels{at}uni-tuebingen.de
- Received 18 October 2007
- Revised 16 January 2008
- Accepted 17 January 2008
- Published Online First 1 February 2008
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 to date.
Objective: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype.
Patients and 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 approximately 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 characterised by spastic paraplegia with mostly subclinical peripheral neuropathy.
Footnotes
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Funding: This study was supported by the German Bundesministerium für Bildung und Forschung (grant 01GM0603-GeNeMove).
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Competing interests: None.
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Ethics approval: The study was approved by the local ethic committee (Vote 277/2004).
