Objectives: To examine the presence of an ATXN2 mutation in patients with parkinsonism in the Korean population and to find the difference in the ATXN2 mutation between ataxic and parkinsonian phenotypes.
Setting: Seoul National University Hospital (a referral center). Patients Patients with Parkinson disease (PD) (n = 468) and the Parkinson variant of multiple system atrophy (MSA-P) (n = 135) who were seen at our Department of Neurology during the past 3 years.
Main outcome measures: CAG expansion in spinocerebellar ataxia type 2 (SCA2) alleles was assessed by polymerase chain reaction amplification and fragment analysis, and its size and interruption were verified by cloning and sequencing. SCA2 was tested also in the family members of the probands. Striatal dopamine transporter (DAT) and D(2) receptor status were evaluated in the probands and their SCA2-positive family members using iodine I 123 [(123)I]-radiolabeled fluoropropyl (FP) 2-carbomethoxy-3-(4-iodophenyl) tropane (CIT) with single-photon emission computed tomography (SPECT) and carbon C 11 [(11)C]-radiolabeled raclopride positron emission tomography (PET).
Results: We found 3 patients with apparently sporadic disease with expanded CAG repeats in the ATXN2 locus. Two patients had a PD phenotype. The third patient showed an MSA-P phenotype. The CAG repeats in the ATXN2 locus of the patients were 35/22, 34/22, and 32/22, respectively (range in normal population, 19-27). The size of repeats was lower than the CAG repeats (38-51) in ataxic SCA2 in our population. The sequence of expanded CAG repeats was interrupted by CAA as (CAG)(n)(CAA)(CAG)(8) in all the patients. DNA analyses in 2 families showed 2 asymptomatic carriers in each family. In the patient with the PD phenotype, striatal DAT loss was more severe in the putamen than the caudate, and [(11)C]raclopride PET showed an increased relative putamen-caudate binding ratio. The patient with the MSA-P phenotype had severe DAT loss throughout the striatum. Two of 3 asymptomatic carriers had striatal DAT loss.
Conclusions: This study demonstrates that SCA2 is one of the genetic causes of PD and MSA-P. All 3 patients had apparently sporadic disease, emphasizing the need to screen even in patients with nonfamilial disease. CAG repeats were in the low expansion range and interrupted by CAA in all patients in the low-range expansion. Therefore, accurate determination of CAG expansion and ATXN2 sequencing are warranted. [(123)I]FP-CIT SPECT and [(11)C]raclopride PET provide a useful way to evaluate the degree of nigrostriatal dopaminergic damage in SCA2-related parkinsonism and gene carriers.