Dctn1 Mutations In Perry Syndrome

Abstract

Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, in which brain pathology is characterized by TDP-43 immunostaining. Through genome-wide linkage analysis we have identified five disease-segregating dynactin (DCTN1) CAP-Gly domain substitutions in 8 families that diminish microtubule binding and lead to intracytoplasmic inclusions. DCTN1 mutations were previously associated with motor neuron disease but can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.