Objective: To further characterize the severity, movement abnormalities, and disease course in an expanded cohort of subjects and their families with XDP and determine if there is a correlation with the presence of single nucleotide polymorphisms (SNPs) in the TAF1 gene.

Background: X-linked dystonia parkinsonism (XDP/DYT3), a neurodegenerative disorder that primarily occurs in Filipino males, is characterized by dystonia and parkinsonism. It is associated with multiple sequence variations in a region of the X chromosome containing several genes, the largest of which encodes the TAF-1 gene. There is phenotypic variability with disease onset, age of onset, and rate and severity of the disease progression. Other factors could contribute to phenotypic variation. The presence or absence of various SNPs in the TAF1 gene may affect the clinical course. In our prior study there was no clear correlation between the presence or absence of SNPs and a distinct XDP phenotype. We recruited more subjects to determine if there is a correlation between genotype and phenotype.

Methods: 40 additional subjects were recruited as an expansion of the cohort first reported at MDS last year, making a total of 78 subjects. 16/78 subjects have the XDP haplotype (12 symptomatic, 4 presymptomatic <21 years of age), 27 obligate carriers, 30 control subjects, 1 possible carrier, and 4 unaffected individuals with varying level risk of developing XDP. 2 members with XDP phenotype are negative for the disease-associated DNA changes. All subjects provided their medical history and were systematically examined using the Burke-Fahn-Marsden and Unified Parkinson’s disease rating scales. Independent raters systematically examined subjects and/or subject videos. Disease severity in confirmed XDP subjects made it impossible to be blinded to their genotype.

Results: In this expanded cohort, no clear correlation was identified between the presence of specific SNPs and a distinct XDP phenotype. Interestingly, one male under the age of 18 displays a recombination event, retaining only a partial XDP haplotype.

Conclusions: A large sample of subjects with XDP and their family members with genetic data regarding the presence of various SNPs in a Filipino control population is needed for definitive genotype-phenotype correlation.

We presented some data last year at MDS. This is an update to the poster presented at MDS that includes the results from the expanded cohort.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-update-on-genotype-phenotype-correlation-in-x-linked-dystonia-parkinsonism-xdpdyt3/