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 p150 Glued 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.