Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterog eneous group of disorders characterized by insidiously progressive spastic weakness in the legs. Genetic loci for autosomal dominant HSP exist on chro mosomes 2p, 14q, and 15q. These loci are excluded in 45% of autosomal domin ant HSP kindreds, indicating the presence of additional loci for autosomal dominant HSP. We analyzed a Caucasian kindred with autosomal dominant HSP a nd identified tight linkage between the disorder and microsatellite markers on chromosome 8q (maximum two-point LOD score 5.51 at recombination fracti on 0). Our results clearly establish the existence of a locus for autosomal dominant HSP on chromosome 8q23-24. Currently this locus spans 6.2 cM betw een D8S1804 and D8S1774 and includes several potential candidate genes. Ide ntifying this novel HSP locus on chromosome 8q23-24 will facilitate discove ry of this HSP gene, improve genetic counseling for families with linkage t o this locus, and extend our ability to correlate clinical features with di fferent HSP loci.