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This Article Full Text Full Text (PDF) web only appendix All Versions of this Article: jnnp.2007.137596v1 79/5/584    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Google Scholar Articles by Schüle, R Articles by Schöls, L PubMed PubMed Citation Articles by Schüle, R Articles by Schöls, L

SPG10 is a rare cause of spastic paraplegia in European families

¹ Hertie-Institute for Clinical Brain Research and Department of Neurology, Eberhard Karls-University Tübingen, Germany
² Department of Neurology, Radboud University Nijmegen Medical Centre, The Netherlands
³ Department of Neurology, University of Ulm, Germany
⁴ Institute for Medical Research, University of Graz, Austria
⁵ Department of Neurology, University of Belgrad, Serbia
⁶ Department of Neurology and Friedrich-Baur-Institute, Ludwig-Maximilians University Munich, Germany
⁷ Department of Neurology, University of Mainz, Germany
⁸ Department of Neurology, Ruhr-University Bochum, Germany
⁹ Department of Neurology, University of Innsbruck, Austria

Correspondence to:
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

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.