title: Extensive white matter involvement in patients with frontotemporal lobar degeneration: think progranulin.
abstract: OBJECTIVE
  Mutations in the progranulin (GRN) gene are responsible for 20% of familial cases of frontotemporal dementias. All cause haploinsufficiency of progranulin, a protein involved in inflammation, tissue repair, and cancer. Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes. We describe 4 GRN mutation carriers with remarkable widespread white matter lesions (WML) associated with lobar atrophy shown on magnetic resonance imaging.
  
  
  METHODS
  Four GRN mutation carriers (age at onset, 56-65 years) presenting with severe WML were selected from 31 GRN mutation carriers who were followed up in our dementia centers. The WML were predominantly in the frontal and parietal lobes and were mostly confluent, affecting the periventricular subcortical white matter and U-fibers. In all patients, common vascular, metabolic, inflammatory, dysimmune, and mitochondrial disorders were excluded and none had severe vascular risk factors.
  
  
  CONCLUSIONS
  Our data suggest that white matter involvement may be linked to progranulin pathological processes in a subset of GRN mutation carriers. The plasma progranulin measurement, which is predictive of GRN mutations, and GRN sequencing should thus be included in investigations of patients with frontotemporal lobar degenerations who show unusual white matter hyperintensities and atrophy on magnetic resonance imaging.
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Paola
authors.initials: P
authors.lastname: Caroppo
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Agnès
authors.initials: A
authors.lastname: Camuzat
authors.affiliation: Centre de Référence des Démences Rares, Hôpital de la Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris (AP-HP), Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Clot
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Lionel
authors.initials: L
authors.lastname: Naccache
authors.affiliation: Laboratoire de biochimie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Foudil
authors.initials: F
authors.lastname: Lamari
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Anne
authors.initials: A
authors.lastname: De Septenville
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.affiliation: Centre Mémoire de Ressource et de Recherche, Service de Neurologie, Centre Hospitalier Universitaire Pontchaillou, Rennes, France12Université de Caen/Basse-Normandie, École Pratique des Hautes Études, INSERM, Unité U1077, Groupement d'Intérêt Public, Cyce.
authors.forename: Serge
authors.initials: S
authors.lastname: Belliard
authors.affiliation: Service de Neurologie et Centres Mémoire de Ressources et de Recherche, Centre Hospitalier Universitaire, Rouen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Olivier
authors.initials: O
authors.lastname: Colliot
authors.affiliation: Institut du Cerveau et de la Moelle Épinière (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM), U 1127, Paris, France2University Pierre and Marie Curie, UMR S975, F-75013, Paris, France3Centre National de la Recherche Scientifique.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D054022:Cerebrum / Q000473:pathology*; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D066127:White Matter / Q000473:pathology*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins