RT Journal Article
SR Electronic
T1 Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1385
OP 1389
DO 10.1212/WNL.0b013e3181a18876
VO 72
IS 16
A1 Kim, J-Y
A1 Kim, S. Y.
A1 Kim, J-M
A1 Kim, Y. K.
A1 Yoon, K-Y
A1 Kim, J. Y.
A1 Lee, B. C.
A1 Kim, J. S.
A1 Paek, S. H.
A1 Park, S. S.
A1 Kim, S. E.
A1 Jeon, B. S.
YR 2009
UL http://n.neurology.org/content/72/16/1385.abstract
AB Objective: To investigate the role of spinocerebellar ataxia type 17 (SCA17) in the development of parkinsonism. Method: We screened 1,155 parkinsonian patients (931 with Parkinson disease and 224 with multiple system atrophy) and 400 normal subjects for SCA17. 99mTc–TRODAT-1 SPECT was used to evaluate the striatal dopamine transporter (DAT) status. Results: Trinucleotide expansion in the SCA17 gene was found in 10 parkinsonian patients (8 with Parkinson disease, 2 with multiple system atrophy) using 42 repeats as an upper normal limit. The repeat sizes in the patients ranged from 43 to 46, which are considered to be low-range expansions. All patients had interrupted sequences. Three probands and three asymptomatic carriers underwent 99mTc–TRODAT-1 SPECT. Striatal DAT binding was markedly reduced in all probands and mildly decreased in one asymptomatic carrier. Among the 400 normal control subjects, there was one individual with an expansion of 44 repeats, another with 43 repeats, and two with 42 repeats. Striatal DAT binding was decreased not only in the control subjects with 44 or 43 repeats, but in ones with 42 repeats, suggesting that an expansion as low as 42 repeats might constitute a susceptibility gene for parkinsonism. Conclusions: Low-range expansion of the SCA17 gene is not a rare genetic cause of parkinsonism without ataxia in our population. Reduced penetrance or variable expressivity in low-range expansion might be an explanation for the blurred cutoff point for normal expansion in SCA17. 123I-FP-CIT=123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane; 99mTc-TRODAT-1=99mTc-2 β[N, N′-bis(2-mercaptoethyl) ethylenediamino] methyl, 3 β-(4-chlorophenyl) tropane; BDI=Beck Depression Inventory; DAT=dopamine transporter; DBS=deep brain stimulation; K-MMSE=Korean version of the Mini-Mental State Examination; MSA=multiple system atrophy; PD=Parkinson disease; PET=positron emission tomography; SCA2=spinocerebellar ataxia type 2; SCA17=spinocerebellar ataxia type 17; STN=subthalamic nucleus; TBP=TATA-binding protein; TNR=trinucleotide repeat; UMSARS=Unified Multiple System Atrophy Rating Scale.