title: DCTN1 mutations in Perry syndrome.
abstract: Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.
authors.affiliation: Division of Neurogenetics, Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida 32224, USA. farrer.matthew@mayo.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Mary M
authors.initials: MM
authors.lastname: Hulihan
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kachergus
authors.forename: Justus C
authors.initials: JC
authors.lastname: Dächsel
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: Linda L
authors.initials: LL
authors.lastname: Grantier
authors.forename: Susan
authors.initials: S
authors.lastname: Calne
authors.forename: Donald B
authors.initials: DB
authors.lastname: Calne
authors.forename: Bernard
authors.initials: B
authors.lastname: Lechevalier
authors.forename: Francoise
authors.initials: F
authors.lastname: Chapon
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Ludwig
authors.initials: L
authors.lastname: Gutmann
authors.forename: Bülent
authors.initials: B
authors.lastname: Elibol
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: Christian
authors.initials: C
authors.lastname: Wider
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Laura A
authors.initials: LA
authors.lastname: Brown
authors.forename: Monica
authors.initials: M
authors.lastname: Castanedes-Casey
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000072159:Dynactin Complex; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007040:Hypoventilation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D013577:Syndrome; D015431:Weight Loss / Q000235:genetics
chemical_list: C000606360:DCTN1 protein, human; D004268:DNA-Binding Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins