title: Parkinsonism and distinct dementia patterns in a family with the MAPT R406W mutation.
abstract: BACKGROUND
  The Arg406Trp (R406W) missense mutation in the microtubule-associated protein-tau gene (MAPT) is a known cause of early-onset dementia. Various dementia phenotypes have been described, including frontotemporal dementia (FTD), FTD with parkinsonism, and early-onset Alzheimer disease (EOAD)-like presentations.
  
  
  METHODS
  Using whole-exome capture with subsequent sequencing, we identified the R406W mutation in a family with multiple individuals with clinically diagnosed EOAD, in a pattern suggesting autosomal dominant inheritance. We reevaluated all available family members clinically.
  
  
  RESULTS
  Each of the affected individuals had a course meeting clinical criteria for EOAD. Two distinct disease trajectories were apparent: one rapidly progressive, and the other long and gradual. Four of five affected individuals also manifested parkinsonian symptoms. FTD features were not prominent and, when present, appeared only late in the course of dementia.
  
  
  CONCLUSIONS
  The MAPT R406W mutation is associated with EOAD-like symptoms and parkinsonism without FTD, as well as distinct cognitive courses.
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carney
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kohli
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Kunkle
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Naj
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA; University of Miami, Miller School of Medicine, Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA; University of Miami, Miller School of Medicine, Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Züchner
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, FL, USA; University of Miami, Miller School of Medicine, Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA. Electronic address: mpericak@med.miami.edu.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000235:genetics* / Q000503:physiopathology*; D018450:Disease Progression; D005190:Family; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Dementia; Early-onset Alzheimer's disease; Frontotemporal dementia; Microtubule-associated protein-tau; Whole-exome sequencing