title: DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes.
abstract: OBJECTIVE
  Progressive supranuclear palsy (PSP) is usually sporadic, but few pedigrees with familial clustering of PSP-like phenotypes have been described. Occasionally, MAPT, C9ORF72, and TARDBP mutations have been identified.
  
  
  OBJECTIVE
  To analyze the DCTN1 gene in 19 families with a clinical phenotype of PSP (PSP-like phenotype).
  
  
  METHODS
  Sequencing of the DCTN1 gene in familial forms of PSP at a referral center among 21 patients with familial PSP-like phenotypes. In addition, 8 patients and relatives from a family carrying a DCTN1 mutation were evaluated.
  
  
  METHODS
  Identification of the DCTN1 mutation and clinical description of DCTN1 mutation carriers.
  
  
  RESULTS
  We identified a DCTN1 mutation in a large family characterized by high intrafamilial clinical phenotype variability. Two patients had PSP-like phenotypes with dystonia, vertical gaze slowness, dysexecutive syndrome, predominant axial rigidity, and midbrain atrophy on brain magnetic resonance imaging. The other patients manifested Perry syndrome, isolated parkinsonism, or a predominant behavioral variant of frontotemporal dementia.
  
  
  CONCLUSIONS
  Mutations of the DCTN1 gene have been previously associated with amyotrophic lateral sclerosis and with Perry syndrome, a rare autosomal dominant disorder characterized by weight loss, parkinsonism, central hypoventilation, and psychiatric disturbances. Our study demonstrates that DCTN1 mutations should be searched for in patients with clinical PSP-like phenotypes and a behavioral variant of frontotemporal dementia, especially when a familial history of dementia, psychiatric disturbances, associated parkinsonism, or an autosomal dominant disorder is present.
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Paola
authors.initials: P
authors.lastname: Caroppo
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital de la Pitié-Salpêtrière, Centre de Référence des Démences Rares, Paris, France6AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique et Cytogénétique, Unité Fonctionnelle de Neurogénétique.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Clot
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rivaud-Péchoux
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Agnès
authors.initials: A
authors.lastname: Camuzat
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Anne
authors.initials: A
authors.lastname: De Septenville
authors.affiliation: Service de Neurologie, Centre Hospitalier Universitaire (CHU) Guillaume et René Laënnec, Nantes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Boutoleau-Bretonnière
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital de la Pitié-Salpêtrière, Centre de Référence des Démences Rares, Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mourlon
authors.affiliation: Service de Neurologie, CHU, Nancy, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sauvée
authors.affiliation: Service de Neurologie, Centre Hospitalier Universitaire (CHU) Guillaume et René Laënnec, Nantes, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lebouvier
authors.affiliation: Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France5AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bonnet
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Richard
authors.initials: R
authors.lastname: Levy
authors.affiliation: Service de Neurologie, Centre Hospitalier Universitaire (CHU) Guillaume et René Laënnec, Nantes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Vercelletto
authors.affiliation: Université Pierre et Marie Curie Université Paris 06, Unité Mixte de Recherche (UMR)_S975, Paris, France2Institut National de la Santé et de la Récherche Médicale, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, Paris, France3Centre Nat.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods*; D000072159:Dynactin Complex; D005260:Female; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins