1. ¹Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8368, Japan
2. ²Hokuyukai Neurology Hospital, Sapporo, Japan
3. ³Department of General Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
4. ⁴Department of Internal Medicine, Division of Neurology and Stroke Care Unit, Hyogo College of Medicine, Nishinomiya, Japan
5. ⁵Department of Neurology, Graduate School of Medicine, Mie University, Tsu, Japan
6. ⁶Department of Neurology, Graduate School of Medicine, Saga University, Saga, Japan

Correspondence: Hidenao Sasaki, Department of Neurology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8368, Japan. E-mail: hsasaki@med.hokudai.ac.jp

^*Rehana Basri, Ichiro Yabe and Hiroyuki Soma have contributed equally to this work.

Received 28 February 2006; Accepted 7 April 2006; Published online 21 June 2006.

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 (1447AG, 1207CG) 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.