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 clinicall y 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 genome-wide 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 s core of 3.61 at D12S1691, allowing us to assign a new locus for ADPHSP (a l ocus that we have designated "SPG10") to this region. Haplotype constructio n 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 furthe r family in which linkage to all five known ADPHSP loci has been excluded.