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C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?
C Sellier1, P Corcia2, P Vourc'h3
1Centre de recherches en biomédecine de Strasbourg, UMR-S1329, Inserm, université de Strasbourg, Strasbourg, France.
Abstract:
The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype-phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE.
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