A new locus for autosomal dominant "pure" hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity.
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.
Reid
E
E
Department of Medical Genetics, University of Cambridge, Cambridge CB2 2XY, United Kingdom.
Dearlove
A M
AM
Rhodes
M
M
Rubinsztein
D C
DC
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
D005819:Genetic Markers