title: Paraplegin mutations in sporadic adult-onset upper motor neuron syndromes.
abstract: OBJECTIVE
  To investigate the frequency of autosomal recessive paraplegin mutations in patients with sporadic adult-onset upper motor neuron (UMN) syndromes.
  
  
  METHODS
  We analyzed the paraplegin gene in 98 Dutch patients with a sporadic adult-onset UMN syndrome. Inclusion criteria were a progressive UMN syndrome, adult onset, duration >6 months, and negative family history. Exclusion criteria were clinical or electrophysiologic evidence of lower motor neuron loss and evidence of other causes using a predefined set of laboratory tests, including analysis of the spastin gene.
  
  
  RESULTS
  Seven patients had homozygous or compound heterozygous pathogenic paraplegin mutations: six patients had UMN symptoms restricted to the legs and one had UMN symptoms in legs and arms. No mutations were found in the 33 patients with UMN involvement of the bulbar region. Age at onset was lower in the seven patients with paraplegin mutations (37 years, range 34-42) than in the 91 patients without mutations (51 years, range 18-77, p = 0.001). Three of the seven patients with paraplegin mutations and none of the patients without mutations developed cerebellar signs during follow-up.
  
  
  CONCLUSIONS
  Paraplegin mutations are a frequent cause of sporadic spastic paraparesis.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. f.brugman@umcutrecht.nl
authors.forename: F
authors.initials: F
authors.lastname: Brugman
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: J H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: W M
authors.initials: WM
authors.lastname: Nillesen
authors.forename: M
authors.initials: M
authors.lastname: de Visser
authors.forename: E
authors.initials: E
authors.lastname: Aronica
authors.forename: J H
authors.initials: JH
authors.lastname: Veldink
authors.forename: L H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000235:genetics*; D009154:Mutation; D020336:Paraparesis, Spastic / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D008666:Metalloendopeptidases; C112889:SPG7 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities