A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34

Hereditary spastic paraplegia (HSP) comprises a group of clinically and gen etically heterogeneous disorders causing progressive spasticity and weaknes s of the lower limbs. We report a large family of French descent with autos omal dominant pure HSP. We excluded genetic linkage to the known loci causi ng HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on chromosome 2q24-q34: a maximum LOD s core of 3.03 was obtained for marker D2S2318. By comparison with families h aving linkage to the major locus of pure autosomal dominant HSP (SPG4 on ch romosome 2p), there were significantly more patients without Babinski signs , with increased reflexes in the upper limbs, and with severe functional ha ndicaps.