Pure Familial Spastic Paraplegia: Clinical and Genetic Analysis of Nine Belgian Pedigrees

We ascertained 9 multigeneration Belgian families with pure dominant spastic paraplegia (SPG) for clinical and genetic studies. Linkage was examined using simple tandem repeat (STR) markers located near the 5 loci for familial SPG on chromosomes Xq28 (SPG1), Xq21.3–q22 (SPG2), 2p21–p24 (SPG4), 14q12–q23 (SPG3) and 15q11.1 (SPG6). Positive linkage results were obtained only for markers at the SPG4 locus mapping the SPG4 gene between D2S400 and D2S367, a region of 4 cM. In order to facilitate the positional cloning of the SPG4 gene, we constructed a contiguous YAC map covering the SPG4 candidate region. Our physical mapping data indicate that the SPG4 gene resides within maximal 5 Mb.