title: Four mutations of the spastin gene in Japanese families with spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
authors.forename: Rehana
authors.initials: R
authors.lastname: Basri
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Soma
authors.affiliation: Hokuyukai Neurology Hospital, Sapporo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Takei
authors.affiliation: Department of Internal Medicine, Division of Neurology and Stroke Care Unit, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Machino
authors.affiliation: Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kokubo
authors.affiliation: Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kosugi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
authors.forename: Ryuichirou
authors.initials: R
authors.lastname: Okada
authors.affiliation: Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yukitake
authors.affiliation: Department of General Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Tachibana
authors.affiliation: Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuzuhara
authors.affiliation: Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan. hsasaki@med.hokudai.ac.jp.
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human