title: Autosomal dominant spastic paraplegia linked to chromosome 2p: clinical and genetic studies of a large Japanese pedigree.
abstract: Autosomal dominant spastic paraplegia (ADSP) is a genetically heterogenous disorder. To date, 3 loci of ADSP have been identified on chromosome 2p, 14q, and 15q, but specific gene mutations remain unknown. To determine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 individuals clinically examined, 15 were affected. The main feature in the affected individuals was a slowly progressive spastic paraplegia, associated with upper limb hyperreflexia (58%), reduction of vibration sense (27%) and bladder disturbance (13%). Age at onset ranged from 13 to 50 years with a mean of 30.3 +/- 14.2 (SD). There were 6 parent-child pairs with anticipation and at least 3 others with 'anti-anticipation'. Linkage with 14q and 15q ADSP loci was excluded, and a highly significant lod score was obtained only in the case of the 2p locus (Zmax = 3.53 for D2S400/D2S352, at theta = 0.00). Our study is the first to confirm the existence of 2p-linked ADSP in the Japanese. There is a significant variety in age at onset and disease severity in these 2p-linked families, but the implication for underlying ADSP mutation is not clear.
authors.affiliation: Department of Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: A
authors.initials: A
authors.lastname: Wakisaka
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: F
authors.initials: F
authors.lastname: Moriwaka
authors.forename: K
authors.initials: K
authors.lastname: Tashiro
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002889:Chromosomes, Human, Pair 2; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007564:Japan; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*