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Abstract Details

Prevalence of Dystonia-Parkinsonism Gene Variants in Individuals with Parkinsonism and Normal Dopamine Transporter Imaging
Movement Disorders
S32 - Movement Disorders: Dystonia and Tremor Disorders (5:18 PM-5:30 PM)
010

Parkinson’s disease (PD) is the most common cause of parkinsonism in older adults. However, up to 15% of individuals initially diagnosed with PD have normal DAT scans; these cases are termed scans without evidence of dopaminergic deficits (SWEDD). While it is understood that the etiology of parkinsonism in individuals with SWEDD is not due to PD, the causes of parkinsonism in SWEDDs are still unclear. One area of interest is the extent to which genetic causes of parkinsonism can mimic PD. We aimed to identify whether variants in dystonia-parkinsonism-related genes are possible etiologies of parkinsonism in SWEDDs.

To determine if there are genetic etiologies for dystonia-parkinsonism among individuals diagnosed with parkinsonism with normal dopamine transporter (DAT) SPECT scans.

Data were from the Parkinson Progression Markers Initiative (PPMI), a multisite, observational study of early PD and healthy controls (HC). Cohorts included: PD (PD) (n=423), parkinsonism with SWEDD (n=64), and healthy controls (HC) (n=196). Whole genome sequencing data were screened for rare, predicted functional variants in dystonia-parkinsonism genes. Comparison of genotype prevalence in SWEDD, PD, and HC groups, minor allele frequency, and reported and predicted function were used to determine the potential significance of variants. For each case with a reported pathogenic variant or one predicted to be functionally relevant, clinical, and imaging data were reviewed.

Eight out of 64 SWEDD patients had a likely deleterious variant in the following genes: PRKRA, SGCE, GLB1, ADCY5, SLC6A3, and GCDH. Average age of symptoms onset was 55.08 (SD=8.64) years, 87.5% were female, and average MDS-UPDRS-3 (motor) score was 11.5 (SD=6.61). 

Genetic abnormalities in dystonia-parkinsonism genes occur in 12.5% individuals with parkinsonism and normal DAT scans (SWEDDs). It is important to consider genetic dystonic disorders as a possible etiology in SWEDD patients for appropriate clinical diagnosis and management. 

Authors/Disclosures
Yajing Yan Yan Xiong (UPMC neurology)
PRESENTER
Dr. Xiong has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Tatiana Foroud (Indiana University School of Medicine) The institution of Dr. Foroud has received research support from NIH. The institution of Dr. Foroud has received research support from Michael J. Fox Foundation. The institution of Dr. Foroud has received research support from Parkinson Foundation. Dr. Foroud has received personal compensation in the range of $500-$4,999 for serving as a Member of an Advisory Committee with Mayo Clinic, University of Pennsylvania, Allen Institute, Mt. Sinai, Van Andel Institute.
Lana Chahine (University of Pittsburgh) Dr. Chahine has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gray Matters Technology. The institution of Dr. Chahine has received research support from UPMC. The institution of Dr. Chahine has received research support from MJFF. The institution of Dr. Chahine has received research support from Denali/Biogen. Dr. Chahine has received publishing royalties from a publication relating to health care.