title: Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia.
abstract: We evaluated seven families segregating pure, autosomal dominant familial spastic paraplegia (SPG) for linkage to four recently identified SPG loci on chromosomes 2q (1), 8q (2), 12q (3), and 19q (4). These families were previously shown to be unlinked to SPG loci on chromosomes 2p, 14q, and 15q. Two families demonstrated linkage to the new loci. One family (family 3) showed significant evidence for linkage to chromosome 12q, peaking at D12S1691 (maximum lod = 3.22). Haplotype analysis of family 3 did not identify any recombinants among affected individuals in the 12q candidate region. Family 5 yielded a peak lod score of 2.02 at marker D19S868 and excluded linkage to other known SPG loci. Haplotype analysis of family 5 revealed several cross-overs in affected individuals, thereby potentially narrowing the SPG12 candidate region to a 5-cM region between markers D19S868 and D19S220. Three of the families definitively excluded all four loci examined, providing evidence for further genetic heterogeneity of pure, autosomal dominant SPG. In conclusion, these data confirm the presence of SPG10 (chromosome 12), potentially reduce the minimum candidate region for SPG12 (chromosome 19q), and suggest there is at least one additional autosomal dominant SPG locus.
authors.affiliation: Department of Medicine, Center for Human Genetics, Duke University Medical Center, CARL Building, Box 3445, Durham, NC 27710, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ashley-Koch
authors.forename: E R
authors.initials: ER
authors.lastname: Bonner
authors.forename: P C
authors.initials: PC
authors.lastname: Gaskell
authors.forename: S G
authors.initials: SG
authors.lastname: West
authors.forename: R
authors.initials: R
authors.lastname: Tim
authors.forename: C M
authors.initials: CM
authors.lastname: Wolpert
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: C D
authors.initials: CD
authors.lastname: Farrell
authors.forename: M
authors.initials: M
authors.lastname: Nance
authors.forename: I K
authors.initials: IK
authors.lastname: Svenson
authors.forename: D A
authors.initials: DA
authors.lastname: Marchuk
authors.forename: R M
authors.initials: RM
authors.lastname: Boustany
authors.forename: J M
authors.initials: JM
authors.lastname: Vance
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002888:Chromosomes, Human, Pair 19; D002889:Chromosomes, Human, Pair 2; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D005819:Genetic Markers