An intronic GGGGCC repeat expansion in c9orf72 gene has been identified as the most common genetic cause of frontotemporal lobar dementia (FTLD), amyotrophic lateral sclerosis (ALS) and FTLD-ALS. The discovery of c9orf72 gene has led to important scientific progresses and has considerably changed our clinical practice over the last few years. This paper summarizes the common and less typical phenotypes associated with c9orf72 expansion, the complex pathological pattern characterized by p62/dipeptide repeat aggregates, as well as the pathological mechanisms by which the expansion might produce neurodegeneration implicating loss-of-function, RNA toxicity, RNA-binding protein sequestration and accumulation of dipeptide repeats. We also discuss the recommendations and limits for genetic testing and counseling in clinical practice.
Keywords: ALS; C9ORF72; DLFT; DLFT-SLA; Dipeptide repeats; Démence lobaire frontotemporale; FTLD; FTLD-ALS; Foci d’ARN; Frontotemporal dementia; Loss-of-function; MAPT; PGRN; Perte de fonction; RNA foci; Répétition de dipeptides; SLA; Sclérose latérale amyotrophique; TDP-43.
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