title: Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11).
abstract: BACKGROUND
  Hereditary spastic paraplegia (HSP) with thin corpus callosum (CC) is a rare neurodegenerative disorder classified as a complicated form of spastic paraplegia. Some patients with HSP with thin CC have previously been described in Japanese families, and the genetic locus was linked to chromosome 15q13-15.
  
  
  OBJECTIVE
  Our objective was to further clinically and genetically characterize HSP with thin CC.
  
  
  METHODS
  We describe the clinical, structural, and functional follow-up and the genetic characterization of 2 sisters aged 26 and 31 years who had severe spastic paraplegia and cognitive impairment.
  
  
  RESULTS
  Magnetic resonance imaging revealed a thin CC with progressing frontoparietal cortical atrophy paralleled by cognitive decline. Using transcranial magnetic stimulation, we delineated a lack of transcallosal inhibition. Images obtained with(18)fluorodeoxyglucose positron emission tomography showed reduced cortical and thalamic hypometabolism that decreased further within 4 years. Additionally, combined axonal loss and demyelinating sensorimotor polyneuropathy were present. Because other family members were not affected, autosomal recessive inheritance was considered likely. Genetic analysis of this autosomal recessive HSP was consistent with the linkage to 15q13-15 (markers D15S971, D15S118, D15S994, and D15S659). No mutation was found within the SLC12A6 gene.
  
  
  CONCLUSIONS
  Progressive axonal degeneration occurs in the corticocortical projections, corticospinal tract, and peripheral nerves in HSP with thin CC linking to chromosome 15q13-15 in a German pedigree.
authors.affiliation: Department of Neurology, University of Regensburg, Universitätsstrasse 84, D-93053 Regensburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
authors.forename: Goekhan
authors.initials: G
authors.lastname: Uyanik
authors.forename: Claudia
authors.initials: C
authors.lastname: Gross
authors.forename: Max
authors.initials: M
authors.lastname: Lange
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schulte-Mattler
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuierer
authors.forename: Joerg
authors.initials: J
authors.lastname: Marienhagen
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.forename: Juergen
authors.initials: J
authors.lastname: Winkler
mesh_terms: D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D011115:Polyneuropathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014055:Tomography, Emission-Computed