title: Possible anticipation in hereditary spastic paraplegia type 4 (SPG4).
abstract: OBJECTIVE
  We report a multigenerational family with uncomplicated hereditary spastic paraplegia type 4 and apparent anticipation. Genetic analysis of the proband revealed a frame shift mutation (5 base pair deletion) in exon 9 of the SPG4 gene encoding the spastin protein. We hypothesized that this deletion mutation may be dynamic and variability in the size of the deletion could account for the anticipation.
  
  
  METHODS
  Clinical and genetic analysis of this family and the deletion mutation.
  
  
  RESULTS
  In this family, the age of onset, which ranges from 3 to 50 years shows an average decrease in the age of onset of 21.8 years per transmission over three generations. Genetic analysis of multiple family members indicates that all affected members carry the same c.1340_1344delTATAA mutation and that it is not dynamic.
  
  
  CONCLUSIONS
  In this family, other molecular mechanisms may contribute to development of anticipation.
authors.affiliation: New Jersey Neuroscience Institute, JFK Medical Center, Edison, New Jersey 08820, USA.
authors.forename: P Leema
authors.initials: PL
authors.lastname: Reddy
authors.forename: William K
authors.initials: WK
authors.lastname: Seltzer
authors.forename: Raji P
authors.initials: RP
authors.lastname: Grewal
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D020132:Anticipation, Genetic / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human