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 vertical bar] N-omega-Fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-tropane ([123 vertical bar] 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 vertical bar] FP-CIT) SPECT was abnormal in the patients and normal in the asymptomatic carriers. Conclusion: 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.