FUS Mutations in Frontotemporal Lobar Degeneration with Amyotrophic Lateral Sclerosis

Article type: Short Communication

Authors: Broustal, Oriane^{a; 1} | Camuzat, Agnès^{a; 1} | Guillot-Noël, Lena^a | Guy, Nathalie^{b; c} | Millecamps, Stéphanie^a | Deffond, Didier^{b; d} | Lacomblez, Lucette^e | Golfier, Véronique^f | Hannequin, Didier^g | Salachas, François^e | Camu, William^h | Didic, Miraⁱ | Dubois, Bruno^{e; j; k; l} | Meininger, Vincent^e | Ber, Isabelle Le^{a; e; k} | Brice, Alexis^{a; e; j; k; m; *} | the French clinical and genetic research network on FTD/FTD-MND, ²

Affiliations: [a] CRicm INSERM UMRS_975, Hôpital de la Pitié-Salpêtrière, Paris, France | [b] Service de neurologie et, CHU de Clermont-Ferrand, France | [c] U929 - Neurobiologie de la Douleur Trigéminale- faculté de chirurgie Dentaire de Clermont Ferrand- Hopital Estaing- Clermont Ferrand, France | [d] CMRR CHU de Clermont-Ferrand, France | [e] Département des maladies du système nerveux, Hôpital de la Pitié-Salpêtrière, Paris, France | [f] Service de neurologie, CHU Pontchaillou, Rennes, France | [g] INSERM U614 & Département de Neurologie, CHU Charles Nicolle, Rouen, France | [h] Service de Neurologie, CHU Guy de Chauliac, Montpellier, France | [i] Service de Neurologie & Neuropsychologie, Hôpital de la Timone, et INSERM U751, Université de la Méditerranée, Marseille, France | [j] Centre de Référence des Démences Rares, Hôpital de la Pitié-Salpêtrière, Paris, France | [k] Université Pierre et Marie Curie, Paris, France | [l] INSERM U610, Hôpital de la Salpêtrière, Paris, France | [m] Département de Génétique, Cytogénétique et Embryologie, Hôpital de la Salpêtrière, Paris, France

Correspondence: [*] Correspondence to: Pr Alexis Brice, Fédération de Neurologie, Hôpital de la Salpêtrière, 47, Boulevard de l'hôpital, 75 651 Paris Cedex 13, France. E-mail: alexis.brice@upmc.fr.

Note: [1] These authors contributed equally to this work.

Note: [2] The French clinical and genetic research network on FTD/FTD-MND includes: Alexis Brice (Hôpital de la Salpêtrière, Paris), Frédéric Blanc (Hôpitaux Civils, Strasbourg), Françoise Clerget-Darpoux (Hôpital Paul Brousse, Villejuif), William Camu (CHU Gui de Chauliac, Montpellier), Philippe Corcia (CHU Tours), Philippe Couratier (CHU Dupuytren, Limoges), Mira Didic (CHU La Timone, Marseille), Bruno Dubois (Hôpital de la Salpêtrière, Paris), Charles Duyckaerts (Hôpital de la Salpêtrière, Paris), Marie-Odile Habert (Hôpital de la Salpêtrière, Paris), Véronique Golfier (CHU Pontchaillou, Rennes), Eric Guedj (CHU La Timone, Marseille), Didier Hannequin (CHU Charles Nicolle, Rouen), Lucette Lacomblez (Hôpital de la Salpêtrière, Paris), Isabelle Le Ber (Hôpital de la Salpêtrière, Paris), Richard Levy (CHU St Antoine, Paris), Vincent Meininger (Hôpital de la Salpêtrière, Paris), Bernard-François Michel (CH Sainte-Marguerite, Marseille), Florence Pasquier (CHU Roger Salengro, Lille), Catherine Thomas-Anterion (CHU Bellevue, Saint-Etienne), Michèle Puel (CHU Rangueil, Toulouse), François Salachas (Hôpital de la Salpêtrière, Paris), François Sellal (CH Colmar), Martine Vercelletto (CHU Laennec, Nantes), Patrice Verpillat (Hôpital de la Salpêtrière, Paris).

Note: [] Handling Associate Editor: Amalia Bruni

Abstract: Rapid advances were made in the knowledge of amyotrophic lateral sclerosis (ALS) with the recent identification of TARDBP and FUS mutations in familial ALS. More recently, FUS-positive inclusions were found in a subset of TDP-43-negative frontotemporal lobar degeneration (FTLD) prompting us to analyze FUS in FTLD and FTLD-ALS patients. The p.Arg521His mutation was identified in a patient who initially had behavioral disorders and rapidly developed ALS. Although the frequency of mutations is low, our study enlarges the phenotypes associated with FUS mutations and shows that FUS could also play a direct pathogenic role in FTLD spectrum of diseases.

Keywords: Amyotrophic lateral sclerosis, frontotemporal dementia, frontotemporal lobar degeneration, FUS, FUS/TLS, MND, TARDBP, TDP-43

DOI: 10.3233/JAD-2010-100837

Journal: Journal of Alzheimer's Disease, vol. 22, no. 3, pp. 765-769, 2010