DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes

Paola Caroppo, Isabelle Le Ber, Fabienne Clot, Sophie Rivaud-Péchoux, Agnès Camuzat, Anne De Septenville, Claire Boutoleau-Bretonnière, Vanessa Mourlon, Mathilde Sauvée, Thibaud Lebouvier, Anne Marie Bonnet, Richard Levy, Martine Vercelletto, Alexis Brice

Research output: Contribution to journalArticlepeer-review


IMPORTANCE: 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). DESIGN, SETTING, AND PARTICIPANTS: 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. MAINOUTCOMESANDMEASURES: 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 AND RELEVANCE: 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.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalJAMA Neurology
Issue number2
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Fingerprint Dive into the research topics of 'DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes'. Together they form a unique fingerprint.

Cite this