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

Lindquist, SG ; Duno, M ; Batbayli, M ; Puschmann, Andreas LU orcid ; Braendgaard, H ; Mardosiene, S ; Svenstrup, K ; Pinborg, LH ; Vestergaard, K and Hjermind, LE , et al. (2013) In Clinical Genetics 83(3). p.279-283
Abstract
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.... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyotrophic lateral sclerosis, corticobasal degeneration, frontotemporal dementia, gait disorders/ataxia, genetics, neurodegeneration, parkinsonism
in
Clinical Genetics
volume
83
issue
3
pages
279 - 283
publisher
Wiley-Blackwell
external identifiers
  • wos:000315098600013
  • scopus:84874019770
  • pmid:22650353
ISSN
0009-9163
DOI
10.1111/j.1399-0004.2012.01903.x
language
English
LU publication?
yes
id
95ca80ae-870a-40b4-9b2f-9d32d25b05c9 (old id 2966088)
date added to LUP
2016-04-01 10:23:14
date last changed
2023-11-09 19:34:17
@article{95ca80ae-870a-40b4-9b2f-9d32d25b05c9,
  abstract     = {{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.}},
  author       = {{Lindquist, SG and Duno, M and Batbayli, M and Puschmann, Andreas and Braendgaard, H and Mardosiene, S and Svenstrup, K and Pinborg, LH and Vestergaard, K and Hjermind, LE and Stokholm, J and Andersen, BB and Johannsen, P and Nielsen, J}},
  issn         = {{0009-9163}},
  keywords     = {{Amyotrophic lateral sclerosis; corticobasal degeneration; frontotemporal dementia; gait disorders/ataxia; genetics; neurodegeneration; parkinsonism}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{279--283}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Clinical Genetics}},
  title        = {{Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease}},
  url          = {{http://dx.doi.org/10.1111/j.1399-0004.2012.01903.x}},
  doi          = {{10.1111/j.1399-0004.2012.01903.x}},
  volume       = {{83}},
  year         = {{2013}},
}