Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease
(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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https://lup.lub.lu.se/record/2966088
- author
- organization
- publishing date
- 2013
- 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}}, }