title: Novel L284R MAPT mutation in a family with an autosomal dominant progressive supranuclear palsy syndrome.
abstract: BACKGROUND
  MAPT mutations are associated with disorders within the frontotemporal lobar degeneration spectrum. The usual presenting syndrome is behavioural variant frontotemporal dementia, although some patients present with parkinsonism. In a number of these cases the dominant clinical features have been consistent with a progressive supranuclear palsy (PSP) syndrome.
  
  
  OBJECTIVE
  To describe a family with an autosomal dominant PSP syndrome with a novel L284R mutation in the MAPT gene.
  
  
  METHODS
  A retrospective case review and genetic analysis of the MAPT gene. A literature review of PSP syndromes associated with mutations in the MAPT gene.
  
  
  RESULTS
  Multiple members of family DRC292 across different generations had a PSP syndrome with 1 member of the family being found to have a novel L284R mutation in the MAPT gene. Behavioural features were also prominent in most cases. A PSP syndrome is only a rare finding associated with MAPT mutations and many of these cases have atypical clinical features.
  
  
  CONCLUSIONS
  Although rare, MAPT mutations should be considered when there is an autosomal dominant family history of a PSP syndrome, particularly of young onset and with prominent behavioural features.
authors.affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rohrer
authors.forename: Dominic
authors.initials: D
authors.lastname: Paviour
authors.forename: Jana
authors.initials: J
authors.lastname: Vandrovcova
authors.forename: John
authors.initials: J
authors.lastname: Hodges
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Martin N
authors.initials: MN
authors.lastname: Rossor
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012189:Retrospective Studies; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins