title: Mutation analysis of SPAST, ATL1, and REEP1 in Korean Patients with Hereditary Spastic Paraplegia.
abstract: OBJECTIVE
  Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders that are characterized by progressive spasticity and weakness of the lower limbs. Mutations in the spastin gene (SPAST) are the most common causes of HSP, accounting for 40-67% of autosomal dominant HSP (AD-HSP) and 12-18% of sporadic cases. Mutations in the atlastin-1 gene (ATL1) and receptor expression-enhancing protein 1 gene (REEP1) are the second and third most common causes of AD-HSP, respectively.
  
  
  METHODS
  Direct sequence analysis was used to screen mutations in SPAST, ATL1, and REEP1 in 27 unrelated Korean patients with pure and complicated HSP. Multiplex ligation-dependent probe amplification was also performed to detect copy-number variations of the three genes.
  
  
  RESULTS
  Ten different SPAST mutations were identified in 11 probands, of which the following 6 were novel: c.760A>T, c.131C>A, c.1351_1353delAGA, c.376_377dupTA, c.1114A>G, and c.1372A>C. Most patients with SPAST mutations had AD-HSP (10/11, 91%), and the frequency of SPAST mutations accounted for 66.7% (10/15) of the AD-HSP patients. No significant correlation was found between the presence of the SPAST mutation and any of the various clinical parameters of pure HSP. No ATL1 and REEP1 mutations were detected.
  
  
  CONCLUSIONS
  We conclude that SPAST mutations are responsible for most Korean cases of genetically confirmed AD-HSP. Our observation of the absence of ATL1 and REEP1 mutations needs to be confirmed in larger series.
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea. ; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Tae-Hyoung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea. ; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Jae-Hyeok
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Park
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea. ; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Neurology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Tai-Seung
authors.initials: TS
authors.lastname: Nam
authors.affiliation: Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Ho-Jung
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Artem
authors.initials: A
authors.lastname: Semenov
authors.affiliation: Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Korea. ; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Kim
keywords: ATL1; Korea; REEP1; SPAST; hereditary spastic paraplegia