Scientists at Brigham and Women’s Hospital and Harvard Medical School in Boston have developed a targeted genetic test for X-linked dystonia-parkinsonism (XDP), a rare movement disorder that primarily affects men of Filipino ancestry. The new test—presented as a poster Saturday during the 2025 Association for Molecular Pathology annual meeting in Boston—focuses on specific DNA changes in the TAF1 gene that have been difficult to detect with standard sequencing methods.
XDP causes symptoms including muscle spasms, tremors, and abnormal postures, often beginning in the face, jaw, or neck, and can progress to impair speech, walking, and independent living. Accurate diagnosis has been challenging because several neurologic conditions share similar features and conventional gene panels or exome sequencing often miss the disease-specific single nucleotide changes (DSCs) associated with XDP.
Eirini Christodoulou, PhD, a clinical fellow in pathology at Harvard University and laboratory genetics and genomics fellow at Brigham and Women’s Hospital, led development of the assay. The test sequences three DSCs in the TAF1 gene to detect the disease-associated haplotype. Validation of the assay included 8 patients previously known to carry the mutation, 7 negative controls, and 3 additional patients suspected of having XDP. The assay correctly identified all positive cases and led to the diagnosis of 2 patients whose prior testing had been negative.
“Our test picked up cases that routine sequencing methods such as exome sequencing and panel testing have missed,” Christodoulou explained. “We need to identify these cases that would otherwise remain hidden and end diagnostic odysseys, particularly in patients whose symptoms overlap with other movement disorders.” Adding XDP-specific testing to the diagnostic workflow may increase diagnosis rates in at-risk populations and reduce the time and cost associated with prolonged diagnostic evaluation, she noted.
Currently, there is no cure for XDP. Management focuses on symptomatic treatment, including medications for movement symptoms, physical and occupational therapy, and, in some cases, deep brain stimulation. Because XDP is strongly linked to families from Panay Island in the Philippines, increased awareness and targeted testing may improve early diagnosis for patients with this ancestry.
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