PAPER

Motor system abnormalities in hereditary spastic paraparesis type 4 (SPG4) depend on the type of mutation in the spastin gene

D Bönsch^1,2, A Schwindt^1,3, P Navratil^1,3, D Palm³, C Neumann¹, S Klimpe^1,4, J Schickel^1,3, J Hazan⁵, C Weiller⁶, T Deufel¹ and J Liepert⁶

¹ Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Germany
² Klinik für Neurologie, Universitätsklinikum Jena
³ Kinderklinik der Universität Münster, Germany
⁴ Neurologische Klinik, Universität Mainz, Germany
⁵ Genoscope, Evry, France
⁶ Klinik für Neurologie, Universität Hamburg, Germany

Correspondence to:
Correspondence to:
Dr D Bönsch, Neurologische Universitätsklinik, Universitätsklinikum Jena, D-07740 Jena, Germany;
dominikus.boensch{at}med.uni-jena.de

Background: Hereditary spastic paraparesis (HSP) denotes a group of inherited neurological disorders with progressive lower limb spasticity as their clinical hallmark; a large proportion of autosomal dominant HSP belongs to HSP type 4, which has been linked to the SPG4 locus on chromosome 2. A variety of mutations have been identified within the SPG4 gene product, spastin.

Objective: Correlation of genotype and electrophysiological phenotype.

Material: Two large families with HSP linked to the SPG4 locus with a very similar disease with respect to age of onset, progression, and severity of symptoms.

Methods: Mutation analysis was performed by PCR from genomic DNA and cDNA, and direct sequencing. The motor system was evaluated using transcranial magnetic stimulation.

Results: Patients differ in several categories depending on the type of mutation present.

Conclusions: For the first time in hereditary spastic paraparesis, a phenotypic correlate of a given genetic change in the spastin gene has been shown.

Keywords: hereditary spastic paraparesis; spastic gene

Abbreviations: HSP, hereditary spastic paraparesis; CMCT, central motor conduction time; PMCT, peripheral motor conduction time; MEP, motor evoked potential; TMS, transcranical magnetic stimulation

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