Citations 2
Clinical, positron emission tomography, and pathological studies of DNAJC13 p.N855S Parkinsonism
Appel‐Cresswell, Silke , Rajput, Ali H. , Thompson, Christina, Silva, Vanessa , McKenzie, Jessamyn , Dinelle, Katherine, McCormick, Siobhan, Vilariño‐Güell, Carles , Stoessl, A. Jon , Dickson, Dennis W. , Robinson, Chris , Farrer, Matthew J. , Rajput, Alex, Sossi, Vesna , Dickson, Dennis W , Appel-Cresswell, Silke
Movement Disorders | September 3, 2014 | Volume: 29 | Issue: 13 | Pages: 1684-1687
AbstractBackgroundFamilies 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.MethodsFamily members were examined clinically longitudinally, and 5 underwent dopaminergic PET imaging. Four family members came to autopsy.ResultsOf 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.ConclusionPD associated with a DNAJC13 p.N855S mutation presents as late‐onset, often slowly progressive, usually dopamine‐responsive typical PD. © 2014 International Parkinson and Movement Disorder Society
In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers
Felício, André C. , Dinelle, Katherine, Agarwal, Pankaj , McKenzie, Jessamyn , Heffernan, Nicole, Road, Jeremy , Appel‐Cresswell, Silke , Farrer, Matthew J. , Schulzer, Michael, Stoessl, A. Jon , Wszołek, Zbigniew K. , Sossi, Vesna , Appel-Cresswell, Silke
Movement Disorders | May 5, 2014 | Volume: 29 | Issue: 9 | Pages: 1197-1201
ABSTRACTIntroductionWe used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome.MethodsAll subjects had brain imaging using 18F‐6‐fluoro‐l‐dopa (FDOPA, dopamine synthesis and storage), (+)‐11C‐dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C‐raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C‐3‐amino‐4‐(2‐dimethylaminomethyl‐phenylsulfanyl)‐benzonitrile (DASB, serotonin transporter).ResultsFDOPA‐PET and DTBZ‐PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC‐PET showed higher uptake in these area. DASB‐PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum.ConclusionsOur data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene. © 2014 International Parkinson and Movement Disorder Society