title: Three novel mutations of the spastin gene in Chinese patients with hereditary spastic paraplegia.
abstract: BACKGROUND
  Hereditary spastic paraplegia is a group of genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity of the lower limbs. The most common form of hereditary spastic paraplegia is caused by mutations in the spastin gene (SPG4), which encodes spastin, an adenosine triphosphatase associated with various cellular activities protein.
  
  
  OBJECTIVE
  To investigate the Chinese patients with hereditary spastic paraplegia for mutations in SPG4.
  
  
  METHODS
  DNA samples from 31 unrelated patients were analyzed for mutations in SPG4 by single-strand conformation polymorphism analysis and direct sequencing. All DNA samples were screened for mutations by the polymerase chain reaction, followed by electrophoresis and silver staining. Each new variant identified was analyzed in 50 control subjects to determine whether it is a polymorphism or a mutation.
  
  
  RESULTS
  Three novel mutations were detected in 4 affected individuals, including 2 missense mutations (T1258A and A1293G) and 1 deletion mutation (1668-1670delCTA).
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of SPG4 mutations in the People's Republic of China. The percentage of involved Chinese families with autosomal dominant hereditary spastic paraplegia with an SPG4 mutation is 18% (4/22), lower than the estimated 40% linked to this locus.
authors.affiliation: National Laboratory of Medical Genetics of China, and the Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China. bstang7398@yahoo.com.cn
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhao
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Long
authors.forename: Heping
authors.initials: H
authors.lastname: Dai
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zi
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis* / Q000235:genetics; D004586:Electrophoresis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology; D000074181:Spastin
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human