title: A familial form of parkinsonism, dementia, and motor neuron disease: a longitudinal study.
abstract: OBJECTIVE
  To describe the clinical, positron emission tomography (PET), pathological, and genetic findings of a large kindred with progressive neurodegenerative phenotypes in which the proband had autopsy-confirmed corticobasal degeneration (CBD).
  
  
  METHODS
  Five family members, including the proband, were examined neurologically. Clinical information from the other family members was collected by questionnaires. Three individuals underwent PET with (11)C-dihydrotetrabenazine and (18)F-fludeoxyglucose. The proband was examined post-mortem. Genetic studies were performed.
  
  
  RESULTS
  The pedigree contains 64 individuals, including 8 affected patients. The inheritance is likely autosomal dominant with reduced penetrance. The proband developed progressive speech and language difficulties at the age of 64 years. Upon examination at the age of 68 years, she showed non-fluent aphasia, word-finding difficulties, circumlocution, frontal release signs, and right-sided bradykinesia, rigidity, and pyramidal signs. She died 5 years after disease onset. The neuropathology was consistent with CBD, including many cortical and subcortical astrocytic plaques. Other family members had progressive neurodegenerative phenotypes - two were diagnosed with parkinsonism and behavioral problems, two with parkinsonism alone, one with amyotrophic lateral sclerosis alone, one with dementia, and one with progressive gait and speech problems. PET on three potentially affected individuals showed no significant pathology. Genetic sequencing of DNA from the proband excluded mutations in known neurodegenerative-related genes including MAPT, PGRN, LRRK2, and C9ORF72.
  
  
  CONCLUSIONS
  Families with such complex phenotypes rarely occur. They are usually associated with MAPT mutations; however, in this family, MAPT mutations have been excluded, implicating another causative gene or genes. Further genetic studies on this family may eventually disclose the etiology.
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Tacik
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Naoya
authors.initials: N
authors.lastname: Aoki
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Strongosky
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Sanchez-Contreras
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.affiliation: Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Department of Physics and Astronomy, University of British Colombia, BC, Canada.
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.affiliation: Department of Neuropathology, Mayo Clinic Florida, Jacksonville, FL, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Pacific Parkinson's Research Centre, Division of Neurology, University of British Colombia & Vancouver Coastal Health, BC, Canada.
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. Electronic address: wszolek.zbigniew@mayo.edu.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000073885:C9orf72 Protein; D003704:Dementia / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D049268:Positron-Emission Tomography; D000077153:Progranulins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D019690:Technetium Tc 99m Exametazime; D013747:Tetrabenazine / Q000031:analogs & derivatives; D015899:Tomography, Emission-Computed, Single-Photon; D016875:tau Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins; C032811:dihydrotetrabenazine; D019690:Technetium Tc 99m Exametazime; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D013747:Tetrabenazine
keywords: Cognitive disorders; Corticobasal degeneration; Dementia; Genetics; PET; Parkinson's disease/Parkinsonism