The silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype

The hereditary spastic paraplegias (HSPs) are a complex group of neurodegen erative disorders characterized by lower-limb spasticity and weakness. Silv er syndrome (SS) is a particularly disabling dominantly inherited form of H SP, complicated by amyotrophy of the hand muscles. Having excluded the mult iple known HSP loci, we undertook a genomewide screen for linkage of SS in one large multigenerational family, which revealed evidence for linkage of the SS locus, which we have designated "SPG17," to chromosome 11q12-q14. Ha plotype construction and analysis of recombination events permitted the min imal interval defining SPG17 to be refined to similar to 13 cM, flanked by markers D11S1765 and D11S4136. SS in a second family was not linked to SPG1 7, demonstrating further genetic heterogeneity in HSP, even within this cli nically distinct subtype.