Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Research output: Contribution to journalJournal articleResearchpeer-review

  • Sg Lindquist
  • M Duno
  • M Batbayli
  • A Puschmann
  • H Braendgaard
  • S Mardosiene
  • K Svenstrup
  • Lh Pinborg
  • K Vestergaard
  • LE Hjermind
  • J Stokholm
  • Bb Andersen
  • P Johannsen
  • Nielsen, Jørgen Erik
Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21-linked frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS). We here report the prevalence of the expansion in a hospital-based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat-primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD-ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD-ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.
Original languageEnglish
JournalClinical Genetics
Volume83
Issue number3
Pages (from-to)279-283
Number of pages5
ISSN0009-9163
DOIs
Publication statusPublished - Mar 2013

ID: 38488977