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.