title: Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion.
abstract: 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.
authors.affiliation: Institut du cerveau et de la moelle épinière (ICM), Inserm U1127, CNRS UMR 7225, Sorbonne Universités, Université Pierre-et-Marie-Curie, université Paris 06, UPMC-P6 UMR S 1127, hôpital Pitié-Salpêtrière, 75013 Paris, France; Centre de référence des rémences rares, hôpital de la Pitié-Salpêtrière, AP-HP, 75013 Paris, France; Département des maladies du système nerveux, hôpital de la Pitié-Salpêtrière, AP-HP, 75013 Paris, France. Electronic address: isabelle.leber@upmc.fr.
authors.forename: I
authors.initials: I
authors.lastname: Le Ber
mesh_terms: D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000073885:C9orf72 Protein; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D019683:Penetrance; D011506:Proteins / Q000235:genetics*; D057177:TDP-43 Proteinopathies / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
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