Four mutations of the spastin gene in Japanese families with spastic paraplegia.
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.
Basri
Rehana
R
Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
Yabe
Ichiro
I
Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
Soma
Hiroyuki
H
Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan.
Takei
Asako
A
Hokuyukai Neurology Hospital, Sapporo, Japan.
Nishimura
Hiroyuki
H
Department of Internal Medicine, Division of Neurology and Stroke Care Unit, Hyogo College of Medicine, Nishinomiya, Japan.
Machino
Yuka
Y
Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
Kokubo
Yasumasa
Y
Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
Kosugi
Masafumi
M
Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
Okada
Ryuichirou
R
Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
Yukitake
Motohiro
M
Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
Tachibana
Hisao
H
Department of General Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Kuroda
Yasuo
Y
Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan.
Kuzuhara
Shigeki
S
Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan.
Sasaki
Hidenao
H
Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, 060-8368, Japan. hsasaki@med.hokudai.ac.jp.
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
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human