Novel Variants in DCTN1 Associated with Perry Disease: A Case Series from a Chinese Parkinsonism Cohort.

BACKGROUND

Perry disease is a rare autosomal dominant inherited neurodegenerative disorder caused by cytoskeleton-associated protein glycine-rich (CAP-Gly) domain-related variants in the DCTN1 gene, with characteristic TDP-43 pathology. The typical manifestations are parkinsonism, psychiatric symptoms, weight loss, and central hypoventilation.

OBJECTIVE

The aim of the study was to delineate the genotypic and phenotypic spectrum of Perry disease in a Chinese parkinsonism cohort.

METHODS

We screened the DCTN1 CAP-Gly domain-related variants in 932 Chinese parkinsonism patients using next-generation sequencing, and functional studies of the identified variants were conducted.

RESULTS

Three variants were detected (two novel: p.Arg32Cys, p.Gly67Ser; one reported: p.Gly71Arg), indicating a rate of 0.32% (3/932). Clinical presentations mimicked progressive supranuclear palsy or early-onset Parkinson's disease. Functional studies supported pathogenicity, revealing impaired localization of DCTN1-encoded p150Glued protein, TDP-43 pathology, and altered lysosomal positioning.

CONCLUSIONS

Our study broadens the genetic and phenotypic spectrum of Perry disease. These findings support consideration of DCTN1 CAP-Gly domain-related variants in patients with parkinsonism to facilitate early recognition and management. © 2026 International Parkinson and Movement Disorder Society.