alpha-Synuclein gene duplication is present in sporadic Parkinson disease.
OBJECTIVE
alpha-Synuclein gene (SNCA) multiplication was found in familial Parkinson disease (PD). We examined SNCA multiplication in patients with familial and sporadic PD and multiple system atrophy (MSA).


METHODS
We screened 1,106 patients with parkinsonism (PD = 906, MSA = 200) for SNCA multiplication by multiplex PCR. Fluorescent in situ hybridization was done to confirm the multiplication. [(123)I]N-omega-Fluoropropyl-2 beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]FP-CIT) SPECT was done in the patients with SNCA multiplication and their family members.


RESULTS
Three patients were identified as having SNCA duplication. One patient had a positive family history, and two patients were sporadic. Each patient had asymptomatic carriers in their families. The familial case had early onset parkinsonism with rapidly progressive course, cognitive impairment, and dysautonomia. Sporadic cases were more typical of PD. [(123)I]FP-CIT SPECT was abnormal in the patients and normal in the asymptomatic carriers.


CONCLUSIONS
SNCA multiplication is present in sporadic Parkinson disease (PD) and needs to be screened. Low penetrance, clinical heterogeneity, and normal dopamine transporter imaging in asymptomatic carriers may suggest the presence of other genetic modifiers or environmental triggers that play a role in the pathogenesis of PD due to SNCA duplication.
Ahn
T-B
TB
Department of Neurology, Kyung Hee University College of Medicine, Korea.
Kim
S Y
SY
Kim
J Y
JY
Park
S-S
SS
Lee
D S
DS
Min
H J
HJ
Kim
Y K
YK
Kim
S E
SE
Kim
J-M
JM
Kim
H-J
HJ
Cho
J
J
Jeon
B S
BS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics; D009154:Mutation; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics; D051844:alpha-Synuclein / Q000235:genetics*
D007457:Iodine Radioisotopes; D014326:Tropanes; D051844:alpha-Synuclein; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane