Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism

Silke Appel-Cresswell; Ali H. Rajput; Vesna Sossi; Christina Thompson; Vanessa Silva; Jessamyn Mckenzie; Katherine Dinelle; Siobhan E. Mccormick; Carles Vilariño-Güell; A. Jon Stoessl; Dennis W. Dickson; Chris A. Robinson; Matthew J. Farrer; Alex Rajput

doi:10.1002/mds.26019

Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism

Silke Appel-Cresswell, Ali H. Rajput, Vesna Sossi, Christina Thompson, Vanessa Silva, Jessamyn Mckenzie, Katherine Dinelle, Siobhan E. Mccormick, Carles Vilariño-Güell, A. Jon Stoessl, Dennis W. Dickson, Chris A. Robinson, Matthew J. Farrer, Alex Rajput

Neuroscience

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization. Methods: Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy. Results: Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology. Conclusion: PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.

Original language	English (US)
Pages (from-to)	1684-1687
Number of pages	4
Journal	Movement Disorders
Volume	29
Issue number	13
DOIs	https://doi.org/10.1002/mds.26019
State	Published - Nov 1 2014

Keywords

DNAJC13
Familial PD
Lewy Body Pathology
Mennonite
Parkinson's disease (PD)
Positron Emission Tomography (PET)

ASJC Scopus subject areas

Neurology
Clinical Neurology

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Appel-Cresswell, S., Rajput, A. H., Sossi, V., Thompson, C., Silva, V., Mckenzie, J., Dinelle, K., Mccormick, S. E., Vilariño-Güell, C., Stoessl, A. J., Dickson, D. W., Robinson, C. A., Farrer, M. J., & Rajput, A. (2014). Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism. Movement Disorders, 29(13), 1684-1687. https://doi.org/10.1002/mds.26019

Appel-Cresswell, S, Rajput, AH, Sossi, V, Thompson, C, Silva, V, Mckenzie, J, Dinelle, K, Mccormick, SE, Vilariño-Güell, C, Stoessl, AJ, Dickson, DW, Robinson, CA, Farrer, MJ & Rajput, A 2014, 'Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism', Movement Disorders, vol. 29, no. 13, pp. 1684-1687. https://doi.org/10.1002/mds.26019

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title = "Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism",

abstract = "Background: Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization. Methods: Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy. Results: Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology. Conclusion: PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.",

keywords = "DNAJC13, Familial PD, Lewy Body Pathology, Mennonite, Parkinson's disease (PD), Positron Emission Tomography (PET)",

author = "Silke Appel-Cresswell and Rajput, {Ali H.} and Vesna Sossi and Christina Thompson and Vanessa Silva and Jessamyn Mckenzie and Katherine Dinelle and Mccormick, {Siobhan E.} and Carles Vilari{\~n}o-G{\"u}ell and Stoessl, {A. Jon} and Dickson, {Dennis W.} and Robinson, {Chris A.} and Farrer, {Matthew J.} and Alex Rajput",

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doi = "10.1002/mds.26019",

language = "English (US)",

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T1 - Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism

AU - Appel-Cresswell, Silke

AU - Rajput, Ali H.

AU - Sossi, Vesna

AU - Thompson, Christina

AU - Silva, Vanessa

AU - Mckenzie, Jessamyn

AU - Dinelle, Katherine

AU - Mccormick, Siobhan E.

AU - Vilariño-Güell, Carles

AU - Stoessl, A. Jon

AU - Dickson, Dennis W.

AU - Robinson, Chris A.

AU - Farrer, Matthew J.

AU - Rajput, Alex

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Background: Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization. Methods: Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy. Results: Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology. Conclusion: PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.

AB - Background: Families of Dutch-German-Russian Mennonite descent with multi-incident parkinsonism have been identified as harboring a pathogenic DNAJC13 p.N855S mutation and are awaiting clinical and pathophysiological characterization. Methods: Family members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy. Results: Of the 16 symptomatic DNAJC13 mutation carriers, 12 had clinically definite, 3 probable, and 1 possible Parkinson's disease (PD). Symptoms included bradykinesia, tremor, rigidity, and postural instability, with a mean onset of 63 years (range, 40-85) and slow progression. Eight of ten subjects who required treatment had a good levodopa response; motor complications and nonmotor symptoms were observed. Dopaminergic PET imaging revealed rostrocaudal striatal deficits typical for idiopathic PD in established disease and subtle abnormalities in incipient disease. Pathological examinations revealed Lewy body pathology. Conclusion: PD associated with a DNAJC13 p.N855S mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical PD.

KW - DNAJC13

KW - Familial PD

KW - Lewy Body Pathology

KW - Mennonite

KW - Parkinson's disease (PD)

KW - Positron Emission Tomography (PET)

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Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism

Abstract

Keywords

ASJC Scopus subject areas

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