• 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, and French Clinical and Genetic Research Network on Frontotemporal Dementia/Frontotemporal Dementia–Amyotrophic Lateral Sclerosis.
• 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.
• JAMA Neurol. 2014 Feb 1; 71 (2): 208-15.

ImportanceProgressive 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.ObjectiveTo analyze the DCTN1 gene in 19 families with a clinical phenotype of PSP (PSP-like phenotype).Design, Setting, And ParticipantsSequencing 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.Main Outcomes And MeasuresIdentification of the DCTN1 mutation and clinical description of DCTN1 mutation carriers.ResultsWe 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 RelevanceMutations 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.

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