title: Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q.
abstract: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of disorders characterized by insidiously progressive spastic weakness in the legs. Genetic loci for autosomal dominant HSP exist on chromosomes 2p, 14q, and 15q. These loci are excluded in 45% of autosomal dominant HSP kindreds, indicating the presence of additional loci for autosomal dominant HSP. We analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage between the disorder and microsatellite markers on chromosome 8q (maximum two-point LOD score 5.51 at recombination fraction 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 between D8S1804 and D8S1774 and includes several potential candidate genes. Identifying this novel HSP locus on chromosome 8q23-24 will facilitate discovery of this HSP gene, improve genetic counseling for families with linkage to this locus, and extend our ability to correlate clinical features with different HSP loci.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109-0940, USA.
authors.forename: P
authors.initials: P
authors.lastname: Hedera
authors.forename: S
authors.initials: S
authors.lastname: Rainier
authors.forename: D
authors.initials: D
authors.lastname: Alvarado
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Williamson
authors.forename: B
authors.initials: B
authors.lastname: Otterud
authors.forename: M
authors.initials: M
authors.lastname: Leppert
authors.forename: J K
authors.initials: JK
authors.lastname: Fink
mesh_terms: D000328:Adult; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology