title: High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia.
abstract: BACKGROUND
  Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. SPG4, SPG3A and SPG31 are the three leading causes of autosomal dominant (AD) HSPs.
  
  
  METHODS
  A total of 20 unrelated AD-HSP families were recruited for clinical and genetic assessment. Detection of mutations in SPG4, SPG3A and SPG31 genes was conducted according to a standard protocol. Genotype-phenotype correlations and determinants for disease severity and progression were analyzed.
  
  
  RESULTS
  Mutations in the SPG4 gene (SPAST) were detected in 18 (90%) of the AD-HSP families. Mutations in SPG4, SPG3A and SPG31 genes were not detected in the remaining two families. Considerable variations in clinical features were noted, even for mutation carriers from the same family. Mutations causing complete loss of the spastin AAA cassette were associated with earlier onset of disease (20 ± 18 years) compared with those with preservation of partial or total AAA cassette (32 ± 19 years, p = 0.041). For those with SPG4 mutations, disease severity was related to the patients' current age, and the progression rate of disease was positively correlated with age at onset.
  
  
  CONCLUSIONS
  SPG4 accounts for most of the AD-HSP cases in Taiwanese, with a frequency significantly higher than in other populations. SPAST mutations which predict complete loss of the spastin AAA cassette were associated with an earlier onset of disease.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Lan
authors.forename: Yung-Yee
authors.initials: YY
authors.lastname: Chang
authors.forename: Tu-Hseuh
authors.initials: TH
authors.lastname: Yeh
authors.forename: Szu-Chia
authors.initials: SC
authors.lastname: Lai
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Hung-Chou
authors.initials: HC
authors.lastname: Kuo
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
authors.forename: Rong-Kuo
authors.initials: RK
authors.lastname: Lyu
authors.forename: Jen-Wen
authors.initials: JW
authors.lastname: Hung
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chang
authors.forename: Chin-Song
authors.initials: CS
authors.lastname: Lu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human