title: C9orf72 and ATXN2 repeat expansions coexist in a family with ataxia, dementia, and parkinsonism.
abstract: Intermediate interrupted ataxin 2 (ATXN2) alleles (27-33 CAG-repeats) increase the risk for amyotrophic lateral sclerosis and are reported as modifiers in chromosome 9 open reading frame 72 (C9orf72) carriers, rendering susceptibility to amyotrophic lateral sclerosis rather than frontotemporal lobar degeneration. The clinical presentation of C9orf72 patients with pathogenic ATXN2 alleles (≥35 CAG-repeats) is unknown.
  
  
  
  Blood samples were collected from a family affected by ataxia, dementia, and parkinsonism, but not amyotrophic lateral sclerosis. Mutation analyses of the proband included C9orf72 and 14 ataxia genes, followed by segregation analyses in family members.
  
  
  
  Both affected siblings carry an uninterrupted 37-repeat expansion in ATXN2 and a methylated G4C2-repeat allele in C9orf72 that is typical of large pathogenic expansions.
  
  
  
  The CAG-expansion in ATXN2 likely caused the ataxia, whereas the dementia may be linked to both C9orf72 and ATXN2 repeat expansions. The pathological uninterrupted ATXN2 repeat may not have the same modifying effect as intermediate interrupted alleles. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zhengrui
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Misquitta
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Sato
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Moreno
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Krembil Neuroscience Center, Movement Disorder's Clinic, Toronto Western Hospital, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Slow
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.|Krembil Neuroscience Center, University Health Network Memory Clinic, Toronto Western Hospital, Ontario, Canada.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Tartaglia
mesh_terms: D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D000067698:Ataxin-2 / Q000235:genetics*; D000073885:C9orf72 Protein / Q000235:genetics*; D003704:Dementia / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D035781:Siblings; D019680:Trinucleotide Repeat Expansion
chemical_list: C000593752:ATXN2 protein, human; D000067698:Ataxin-2; D000073885:C9orf72 Protein
keywords: ALS; ATXN2; C9orf72; ataxia; dementia; parkinsonism