title: The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype.
abstract: The hereditary spastic paraplegias (HSPs) are a complex group of neurodegenerative disorders characterized by lower-limb spasticity and weakness. Silver syndrome (SS) is a particularly disabling dominantly inherited form of HSP, complicated by amyotrophy of the hand muscles. Having excluded the multiple known HSP loci, we undertook a genomewide screen for linkage of SS in one large multigenerational family, which revealed evidence for linkage of the SS locus, which we have designated "SPG17," to chromosome 11q12-q14. Haplotype construction and analysis of recombination events permitted the minimal interval defining SPG17 to be refined to approximately 13 cM, flanked by markers D11S1765 and D11S4136. SS in a second family was not linked to SPG17, demonstrating further genetic heterogeneity in HSP, even within this clinically distinct subtype.
authors.affiliation: Medical Genetics, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Patel
authors.forename: P E
authors.initials: PE
authors.lastname: Hart
authors.forename: T T
authors.initials: TT
authors.lastname: Warner
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
authors.forename: M A
authors.initials: MA
authors.lastname: Patton
authors.forename: S
authors.initials: S
authors.lastname: Jeffery
authors.forename: A H
authors.initials: AH
authors.lastname: Crosby
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006225:Hand / Q000503:physiopathology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology*; D013577:Syndrome
chemical_list: D005819:Genetic Markers