title: Motor system abnormalities in hereditary spastic paraparesis type 4 (SPG4) depend on the type of mutation in the spastin gene.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, D-07740 Jena, Germany. dominikus.boensch@med.uni-jena.de
authors.forename: D
authors.initials: D
authors.lastname: Bönsch
authors.forename: A
authors.initials: A
authors.lastname: Schwindt
authors.forename: P
authors.initials: P
authors.lastname: Navratil
authors.forename: D
authors.initials: D
authors.lastname: Palm
authors.forename: C
authors.initials: C
authors.lastname: Neumann
authors.forename: S
authors.initials: S
authors.lastname: Klimpe
authors.forename: J
authors.initials: J
authors.lastname: Schickel
authors.forename: J
authors.initials: J
authors.lastname: Hazan
authors.forename: C
authors.initials: C
authors.lastname: Weiller
authors.forename: T
authors.initials: T
authors.lastname: Deufel
authors.forename: J
authors.initials: J
authors.lastname: Liepert
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D010641:Phenotype; D012035:Refsum Disease / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D000074181:Spastin
chemical_list: D002135:Calcium-Binding Proteins; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human