title: Spastin mutations in sporadic adult-onset upper motor neuron syndromes.
abstract: Mutation of the spastin gene is the single most common cause of pure hereditary spastic paraparesis. In patients with an unexplained sporadic upper motor neuron (UMN) syndrome, clinical distinction between primary lateral sclerosis and sporadic hereditary spastic paraparesis may be problematic. To investigate whether spastin mutations are present in patients with primary lateral sclerosis and sporadic hereditary spastic paraparesis, we screened the spastin gene in 99 Dutch patients with an unexplained, apparently sporadic, adult-onset UMN syndrome. We found 6 mutations, of which 4 were novel, in the subgroup of 47 patients with UMN symptoms restricted to the legs (13%). Another novel spastin mutation was found in a patient with a rapidly progressive spinal and bulbar UMN syndrome that progressed to amyotrophic lateral sclerosis. In the patients with arm or bulbar UMN symptoms and slow progression, no spastin mutations were found. Our study shows that spastin mutations are a frequent cause of apparently sporadic spastic paraparesis but not of primary lateral sclerosis.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, G03.228, PO Box 85500, 3508 GA Utrecht, the Netherlands. f.brugman@neuro.az.nl
authors.forename: Frans
authors.initials: F
authors.lastname: Brugman
authors.forename: John H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.forename: Martina H A
authors.initials: MH
authors.lastname: Versteeg
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics*; D009154:Mutation; D009426:Netherlands; D020336:Paraparesis, Spastic / Q000235:genetics; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human