title: A new locus for autosomal dominant "pure" hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity.
abstract: Autosomal dominant pure hereditary spastic paraplegia (ADPHSP) is clinically characterized by slowly progressive lower-limb spasticity. The condition is genetically heterogeneous, and loci have been mapped at chromosomes 2p, 8q, 14q, and 15q. We have performed a genomewide linkage screen on a large family with ADPHSP, in which linkage to all four previously known loci was excluded. Analysis of markers on chromosome 12q gave a peak pairwise LOD score of 3.61 at D12S1691, allowing us to assign a new locus for ADPHSP (a locus that we have designated "SPG10") to this region. Haplotype construction and analysis of recombination events narrowed the SPG10 locus to a 9.2-cM region between markers D12S368 and D12S83. In addition, our data strongly suggest that there are at least six ADPHSP loci, since we describe a further family in which linkage to all five known ADPHSP loci has been excluded.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge CB2 2XY, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Reid
authors.forename: A M
authors.initials: AM
authors.lastname: Dearlove
authors.forename: M
authors.initials: M
authors.lastname: Rhodes
authors.forename: D C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010264:Paraplegia / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers