title: Autosomal dominant hereditary spastic paraplegia with axonal sensory motor polyneuropathy maps to chromosome 21q 22.3.
abstract: OBJECTIVE
  Hereditary spastic paraplegia (HSP) are a genetically and clinically heterogeneous group of disorders. At present, 19 autosomal dominant loci for HSP have been mapped. We ascertained an American family of European descent segregating an autosomal dominant HSP associated with peripheral neuropathy.
  
  
  METHODS
  A genome wide scan was performed with 410 microsatellite repeat marker (Weber lab screening set 16) and following linkage and haplotype analysis, fine mapping was performed. Established genes or loci for HSP were excluded by direct sequencing or haplotype analysis.
  
  
  RESULTS
  All established loci for HSP were excluded. Fine mapping suggested a locus on chromosome 21q22.3 flanked by markers D21S1411 and D21S1446 with a maximum logarithm of odds score of 2.05 and was supported by haplotype analysis. A number of candidate genes in this region were analyzed and no disease-producing mutations were detected.
  
  
  CONCLUSIONS
  We present the clinical and genetic analysis of an American family with autosomal dominant HSP with axonal sensory motor polyneuropathy mapping to a novel locus on chromosome 21q22.3 designated SPG56.
authors.affiliation: a 1 The Neuro-genetics Institute, Sharon Hill , PA , USA.
authors.forename: Leema Reddy
authors.initials: LR
authors.lastname: Peddareddygari
authors.affiliation: b 2 New Jersey Neuroscience Institute at JFK Medical Center , Edison , NJ , USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Hanna
authors.affiliation: c 3 Department of Epidemiology and Biostatistics , Case Western Reserve University School of Medicine , Cleveland , OH , USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Igo
authors.affiliation: c 3 Department of Epidemiology and Biostatistics , Case Western Reserve University School of Medicine , Cleveland , OH , USA.|d 4 Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration , Rockville , MA , USA.
authors.forename: Yuqun A
authors.initials: YA
authors.lastname: Luo
authors.affiliation: c 3 Department of Epidemiology and Biostatistics , Case Western Reserve University School of Medicine , Cleveland , OH , USA.|e 5 Graduate School of Public Health, Seoul National University , Seoul , Korea.
authors.forename: Sungho
authors.initials: S
authors.lastname: Won
authors.affiliation: f 6 Department of Neurology , Columbia University , New York , NY , USA.
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.affiliation: g 7 Neuroscience Institute, Saint Francis Medical Center , Trenton , NJ , USA.
authors.forename: Raji P
authors.initials: RP
authors.lastname: Grewal
mesh_terms: D000328:Adult; D000368:Aged; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology
keywords: autosomal dominant; candidate gene analysis; clinical and genetic analysis; family-based linkage analysis; fine mapping; hereditary spastic paraplegia