TY - JOUR
T1 - DCTN1 mutation analysis in families with progressive supranuclear palsy-like phenotypes
AU - Caroppo, Paola
AU - Le Ber, Isabelle
AU - Clot, Fabienne
AU - Rivaud-Péchoux, Sophie
AU - Camuzat, Agnès
AU - De Septenville, Anne
AU - Boutoleau-Bretonnière, Claire
AU - Mourlon, Vanessa
AU - Sauvée, Mathilde
AU - Lebouvier, Thibaud
AU - Bonnet, Anne Marie
AU - Levy, Richard
AU - Vercelletto, Martine
AU - Brice, Alexis
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1001/jamaneurol.2013.5100
DO - 10.1001/jamaneurol.2013.5100
M3 - Article
C2 - 24343258
AN - SCOPUS:84893828881
VL - 71
SP - 208
EP - 215
JO - JAMA Neurology
JF - JAMA Neurology
SN - 2168-6149
IS - 2
ER -