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.
Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B (dHMN7B), Perry syndrome, amyotrophic lateral sclerosis and amyotrophic lateral sclerosis‑frontotemporal dementia.
Recently, we reported colocalization of phosphorylated α-synuclein (p-SNCA) and the largest subunit of dynactin (DCTN1) in Lewy body (LB)-like structures in Perry syndrome.
To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient with F52L mutation in DCTN1, and describe clinical and neuroimaging investigations.
The genetic cause of Perry syndrome was recently identified with five mutations in the dynactin gene (DCTN1) segregating with disease in eight families.
Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation.
Depression, parkinsonism, and hypoventilation (Perry syndrome) or familial motor neuron disease have been linked to mutations in dynactin P150(Glued) (DCTN1).
Point mutations within the CAP-gly domain of the p150(Glued) subunit of the dynactin complex have been identified in patients with distal spinal bulbar muscular atrophy (dSBMA) and Perry's syndrome.
Mutations in dynactin DCTN1 (p150(glued)) have previously been linked to familial motor neuron disease or Perry syndrome (PS) consisting of depression, parkinsonism and hypoventilation.
Perry syndrome due to the DCTN1G71R mutation: a distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure.
To test the hypothesis that the G71A mutation in the DCTN1 gene is sufficient to cause Perry syndrome, we generated DCTN1<sup>G71A</sup> transgenic mice.
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.