Clinicodemographic and Genetic Modifier Correlation in an X-Linked Dystonia-Parkinsonism Cohort from Mindanao

Abstract

Background: X-linked dystonia-parkinsonism (XDP), a neurodegenerative movement disorder endemic to the Philippines, is primarily investigated in patients from Panay Island and the Greater Manila area. However, individuals residing in geographically distant regions may exhibit different clinical or genetic characteristics compared to those documented in earlier reports.

Objective: The aim was to investigate the relationship of XDP clinical features in a Mindanao cohort with modifiers of age at onset (AAO) variability and utilization of a previously reported AAO model.

Methods: We investigated clinical and genetic features in 27 XDP patients from southern Mindanao. In all patients, we genotyped the 4 polymorphisms linked to AAO.

Results: The XDP-relevant hexanucleotide repeat number significantly correlated with AAO in the 27 patients and explained about 68% of AAO variability. There is no statistical difference between the predicted and actual AAO.

Conclusion: The AAO model may provide reliable predictions by employing the effect of XDP genetic modifiers of AAO variability.

Keywords: X‐linked dystonia‐parkinsonism (XDP); age at onset; genetic modifiers; hexanucleotide repeat numbers.

FIG. 1

Genetic analyses in patients from Koronadal. (A) Inverse correlation between AAO (age at onset) and repeat number in the cohort of 27 genetically confirmed XDP (X‐linked dystonia parkinsonism) patients (blue regression line) corresponds to the previously reported findings (red regression line). (B) Correlation between the difference in estimated AAO and actual AAO and repeat number.