title: SPG10 is a rare cause of spastic paraplegia in European families.
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.
  
  
  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.
authors.affiliation: Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str 3, D-72076 Tübingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schüle
authors.forename: B P H
authors.initials: BP
authors.lastname: Kremer
authors.forename: J
authors.initials: J
authors.lastname: Kassubek
authors.forename: M
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: V
authors.initials: V
authors.lastname: Kostic
authors.forename: T
authors.initials: T
authors.lastname: Klopstock
authors.forename: S
authors.initials: S
authors.lastname: Klimpe
authors.forename: S
authors.initials: S
authors.lastname: Otto
authors.forename: S
authors.initials: S
authors.lastname: Boesch
authors.forename: B P
authors.initials: BP
authors.lastname: van de Warrenburg
authors.forename: L
authors.initials: L
authors.lastname: Schöls
mesh_terms: D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D005060:Europe; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D020233:Gait Disorders, Neurologic / Q000175:diagnosis / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D016547:Kinesins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009460:Neurologic Examination; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics*
chemical_list: C500506:KIF5A protein, human; D022821:RNA Splice Sites; D016547:Kinesins