Abstract Details

Title Autosomal-Dominant Parkinsonism Associated with a Newly Described Mutation in DNAJC13: Clinical, Imaging and Pathological Description

Topic Movement Disorders

Presentation(s) S13 - (-)

Poster/Presentation
Number 002

Background We identified a large Saskatchewan multi-incident family with autosomal-dominant parkinsonism and found that a DNAJC13 mutation predisposed to the disease. Two further multi-incident kindreds with PD were identified as well as two seemingly sporadic cases. All are of Mennonite origin.

Objective

Design/Methods Subjects were clinically screened with an interview and a neurological exam and provided DNA samples. Symptomatic carriers were clinically followed longitudinally where possible. PET imaging was performed with dopaminergic tracers (F-dopa, DTBZ, methylphenidate, raclopride). Pathological examination was performed on family members with a clinical diagnosis of PD.

Results 57 subjects were screened in the Saskatchewan family, 16 carried the DNAJC13 mutation. Of these, 11 were symptomatic for PD: four had clinically definite PD, five possible/probable PD, two had historical parkinsonism. The phenotype in those with clinically definite PD was typical for PD including bradykinesia, tremor, rigidity, and postural instability. Motor complications (wearing-off and dyskinesias), and non-motor symptoms typical for PD were observed in some subjects. Subjects had a good response to levodopa therapy. Age of onset of first motor symptoms was 65 years. PET scanning included three mutation carriers, one with clinically definite, one with possible PD, one asymptomatic subject. The subject with clinically definite PD had a dopaminergic presynaptic deficit in the striatum with a rostro-caudal gradient typical for PD. PET imaging in the two other subjects was normal. Pathological examination of three mutation carriers with clinically definite PD revealed Lewy body pathology consistent with PD. One of the subjects also had TDP-43 reactive pathology.

Conclusions The clinical, imaging and pathological presentation of parkinsonism caused by DNAJC13 closely resembles idiopathic PD. The newly discovered gene mutation will be important for the development of pathophysiological models of PD and translational research.

Authors/Disclosures
Silke A. Cresswell, MD (University of British Columbia) PRESENTER	No disclosure on file
Ali H. Rajput, MD, FAAN (Royal Univ Hospital/Dept of Neuro)	No disclosure on file
Michele L. Rajput (SK Centre for PD & MD)	No disclosure on file
	No disclosure on file
	No disclosure on file
Daniel O. Claassen, MD, FAAN (Vanderbilt University Medical Center)	Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Michigan. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
A J. Stoessl, MD, FAAN (UBC)	No disclosure on file
	No disclosure on file
Dennis W. Dickson, MD (Mayo Clinic)	Dr. Dickson has nothing to disclose.
Matthew Farrer, MD (Mayo Clinic Jacksonville)	No disclosure on file
Alexander H. Rajput, MD, FAAN (Royal Univ Hosp/division of Neuro)	Dr. Rajput has received personal compensation in the range of $500-$4,999 for serving as a Peer reviewer with CQDM.

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