Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease. (4th July 2012)

• Record Type: Journal Article
• Authors: Lindquist, SG; Duno, M; Batbayli, M; Puschmann, A; Braendgaard, H; Mardosiene, S; Svenstrup, K; Pinborg, LH; Vestergaard, K; Hjermind, LE; Stokholm, J; Andersen, BB; Johannsen, P; Nielsen, JE
• Is Part Of: Clinical genetics. Volume 83:Number 3(2013:Mar.)
• Page Start: 279
• Page End: 283
• Publication Date: 2012-07-04
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/j.1399-0004.2012.01903.x
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of <italic>C9ORF72</italic> 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 <italic>C9ORF72</italic> 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 <italic>ATXN2</italic>. 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 <italic>ATXN2</italic> repeat sizes. Our study widens the clinical spectrum of <italic>C9ORF72</italic>related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the <italic>ATXN2</italic> gene.</p> </abstract>