title: 'Complicated' autosomal dominant familial spastic paraplegia is genetically distinct from 'pure' forms.
abstract: BACKGROUND
  The familial spastic paraplegias (FSPs) are hereditary neurodegenerative disorders with an unknown pathogenesis. Pure and complicated forms are currently differentiated on clinical grounds. To date, no linkage studies in complicated FSP have been reported, and candidate genes have not been suggested. Three different gene loci responsible for pure autosomal dominant FSP and 1 for pure autosomal recessive FSP recently have been found. This raises the question of whether the complicated forms may also be linked to any of these loci.
  
  
  OBJECTIVE
  To investigate whether complicated autosomal dominant FSP is allelic to any of the pure forms with defined loci.
  
  
  METHODS
  Clinical characterization of a large kindred that included 4 generations and multipoint linkage analyses.
  
  
  METHODS
  Universitätsklinikum Charité, Humboldt-Universität Berlin, Neurologische Klinik und Poliklinik, Berlin, Germany.
  
  
  METHODS
  Twenty-six family members, 13 of whom were affected.
  
  
  RESULTS
  Thirteen members of a large family of 4 generations experienced a slowly progressive syndrome of spastic paraplegia. Hypomimia, bradykinesia, axial and limb rigidity, supranuclear gaze palsy, dysarthria, bladder and sphincter disturbances, cerebellar signs, and epilepsy were noted as additional features in some of the affected individuals. The mean age at onset was 20 years (range, 5-30 years), and the pattern of transmission was compatible with an autosomal dominant mode of inheritance. The CAG-repeat expansions in the spinocerebellar ataxia type 1 and Machado-Joseph disease genes were not found. Linkage analysis with the use of a panel of (AC)n dinucleotide repeat markers from the Généthon map demonstrated exclusion of all 4 FSP loci recently mapped by linkage to pure forms of FSP on chromosomes 14q, 2p, 15q, and 8.
  
  
  CONCLUSIONS
  Complicated FSP in this family is not linked to any of the known pure FSP loci, including the recessive one. Therefore, the clinical differentiation of both forms still is of major relevance.ACKG
authors.affiliation: Neurologische Klinik, Universitätsklinikum Charité, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Meierkord
authors.forename: P
authors.initials: P
authors.lastname: Nürnberg
authors.forename: A
authors.initials: A
authors.lastname: Mainz
authors.forename: K
authors.initials: K
authors.lastname: Marczinek
authors.forename: M
authors.initials: M
authors.lastname: Mrug
authors.forename: J
authors.initials: J
authors.lastname: Hampe
mesh_terms: D000368:Aged; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D018911:Trinucleotide Repeats