DCTN1 mutations in Perry syndrome.
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.
Farrer
Matthew J
MJ
Division of Neurogenetics, Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida 32224, USA. farrer.matthew@mayo.edu
Hulihan
Mary M
MM
Kachergus
Jennifer M
JM
Dächsel
Justus C
JC
Stoessl
A Jon
AJ
Grantier
Linda L
LL
Calne
Susan
S
Calne
Donald B
DB
Lechevalier
Bernard
B
Chapon
Francoise
F
Tsuboi
Yoshio
Y
Yamada
Tatsuo
T
Gutmann
Ludwig
L
Elibol
Bülent
B
Bhatia
Kailash P
KP
Wider
Christian
C
Vilariño-Güell
Carles
C
Ross
Owen A
OA
Brown
Laura A
LA
Castanedes-Casey
Monica
M
Dickson
Dennis W
DW
Wszolek
Zbigniew K
ZK
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
C000606360:DCTN1 protein, human; D004268:DNA-Binding Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins