title: Mutation analysis of SPG4 and SPG3A genes and its implication in molecular diagnosis of Korean patients with hereditary spastic paraplegia.
abstract: BACKGROUND
  Hereditary spastic paraplegia (HSP), a genetically and clinically heterogeneous group of neurodegenerative disorders, is characterized by progressive lower limb weakness and spasticity. Among the 8 loci associated with the autosomal dominant uncomplicated HSP (AD-HSP), the spastin (SPG4) and atlastin (SPG3A) genes have been known to account for approximately 40% and 10% of all cases, respectively.
  
  
  OBJECTIVE
  To investigate the contribution of these 2 genes in the occurrence of HSP in Korean patients.
  
  
  METHODS
  Clinical and genetic study.
  
  
  METHODS
  Tertiary care center.
  
  
  METHODS
  Eighteen patients with uncomplicated HSP (11 AD and 7 sporadic) underwent screening for gene mutation.
  
  
  METHODS
  Mutations in the SPG4 and SPG3A genes as detected by direct sequencing of all coding exons and flanking intronic sequences.
  
  
  RESULTS
  We identified 8 different SPG4 mutations, 7 of which have not been reported elsewhere. Among the detected mutations were 3 missense mutations, 2 in-frame deletions, 2 frameshift mutations, and 1 splice-site mutation. No mutation was found in the SPG3A gene.
  
  
  CONCLUSIONS
  Compared with previous studies, a higher frequency of SPG4 gene mutations in AD-HSP (7/11; 64%) was observed, suggesting that a mutation analysis for the SPG4 gene might be helpful for molecular diagnosis of AD-HSP in Korean patients.
authors: Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Su-Yon
authors: SY
authors: Park
authors: Chang-Seok
authors: CS
authors: Ki
authors: Hee-Jin
authors: HJ
authors: Kim
authors: Jong-Won
authors: JW
authors: Kim
authors: Duk Hyun
authors: DH
authors: Sung
authors: Byoung Joon
authors: BJ
authors: Kim
authors: Won Yong
authors: WY
authors: Lee
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007723:Korea; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015419:Spastic Paraplegia, Hereditary / Q000208:ethnology / Q000235:genetics*; D000074181:Spastin
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human