title: Three families with Perry syndrome from distinct parts of the world.
abstract: OBJECTIVE
  Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1.
  
  
  METHODS
  Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency. Dopaminergic therapy was initiated in probands from two families.
  
  
  RESULTS
  Besides the probands, 17 symptomatic relatives from all families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their fifth or sixth decade of life. Parkinsonism was moderate with a partial response to dopaminergic treatment. All affected persons but two died of respiratory insufficiency. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half-year follow-up examination has revealed that the diaphragmatic pacemaker is optimally functioning without any major complications. In the Colombian and US families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C mutations were identified. In functional assays, both mutations altered microtubule binding consistent with a pathogenic role.
  
  
  CONCLUSIONS
  Perry syndrome is a rare condition, but new cases are expected to be diagnosed worldwide. Early diagnosis prevents life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as an effective symptomatic treatment option.
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Pawel
authors.initials: P
authors.lastname: Tacik
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Fabienne C
authors.initials: FC
authors.lastname: Fiesel
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, United States; Mayo Graduate School, Neurobiology of Disease, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.affiliation: Department of Neurology, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Felipe
authors.initials: F
authors.lastname: Pretelt
authors.affiliation: Department of Neurology, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Camilo
authors.initials: C
authors.lastname: Castañeda Cardona
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Alexa
authors.initials: A
authors.lastname: Kidd
authors.affiliation: Respiratory Services, Christchurch Hospital, Canterbury District Health Board, New Zealand.
authors.forename: Michael
authors.initials: M
authors.lastname: Hlavac
authors.affiliation: Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Anthony
authors.initials: A
authors.lastname: Raizis
authors.affiliation: Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, Gainesville, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Sharleen
authors.initials: S
authors.lastname: Traynor
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Strongosky
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, United States; Mayo Graduate School, Neurobiology of Disease, Mayo Clinic Florida, Jacksonville, United States.
authors.forename: Wolfdieter
authors.initials: W
authors.lastname: Springer
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, United States. Electronic address: Wszolek.Zbigniew@mayo.edu.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D003105:Colombia; D003863:Depression / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D003964:Diaphragm / Q000601:surgery; D000072159:Dynactin Complex; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D007040:Hypoventilation / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009520:New Zealand; D020734:Parkinsonian Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D010375:Pedigree; D014481:United States; D057177:TDP-43 Proteinopathies
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins
keywords: DCTN1; Familial; Gene mutation; Parkinsonism; Perry syndrome; Respiratory insufficiency