title: A Japanese SPG4 family with a novel missense mutation of the SPG4 gene: intrafamilial variability in age at onset and clinical severity.
abstract: OBJECTIVE
  We report the results of clinical and genetic studies on a Japanese SPG4 family.
  
  
  METHODS
  Family N included eight patients in four generations with autosomal dominant transmission. We performed neurological and molecular analyses on the SPG4 gene in the family members comprising three patients, 12 at-risk individuals, and three normal spouses.
  
  
  RESULTS
  The three patients showed pure spastic paraplegia, two of them exhibiting a decrease in vibration sense. There was marked intrafamilial variability in age at onset and clinical severity in the present family. On molecular analysis, a novel missense mutation (nt1579 C-->T) in exon 12 of the SPG4 gene was found in the three patients, three probably affected, and an asymptomatic carrier.
  
  
  CONCLUSIONS
  The present SPG4 family, which was shown to have a novel SPG4 mutation, exhibited marked variability in the clinical features, indicating the participation of additional factors in the phenotypic appearance of this family.
authors.affiliation: Department of Neurology, Jichi Medical School, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Namekawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takiyama
authors.forename: K
authors.initials: K
authors.lastname: Sakoe
authors.forename: H
authors.initials: H
authors.lastname: Nagaki
authors.forename: H
authors.initials: H
authors.lastname: Shimazaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshimura
authors.forename: K
authors.initials: K
authors.lastname: Ikeguchi
authors.forename: I
authors.initials: I
authors.lastname: Nakano
authors.forename: M
authors.initials: M
authors.lastname: Nishizawa
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human