No mutations were found in any of the patients, suggesting that a mutation at the coding region of the alpha-synuclein gene is unlikely to be responsible for nigrostriatal degeneration in typical sporadic Parkinson's disease.
Patients with the alpha-synuclein mutation were significantly younger (mean 7.6 years), showed the first sign of the disease significantly earlier in life (mean 10.8 years), and had significantly longer duration of the disease compared with patients with sPD.
A recent study showed significant association of sporadic Parkinson's disease with a polymorphism within the alpha-synuclein gene and closely linked DNA markers on chromosome 4q and the APOE epsilon4 allele.
Alpha-synuclein accumulates in the brains of sporadic Parkinson's disease patients as a major component of Lewy bodies, and mutations in alpha-synuclein are associated with familial forms of Parkinson's disease.
Alpha-synuclein was implicated in Parkinson's disease when missense mutations in the alpha-synuclein gene were found in autosomal dominant Parkinson's disease and alpha-synuclein was shown to be a major constituent of protein aggregates in sporadic Parkinson's disease and other synucleinopathies.
Mutations in alpha-synuclein gene cause familial form of Parkinson disease, and deposition of wild-type alpha-synuclein as Lewy bodies occurs as a hallmark lesion of sporadic Parkinson disease and dementia with Lewy bodies, implicating alpha-synuclein in the pathogenesis of Parkinson disease and related neurodegenerative diseases.
To extend our previous finding in a larger sample and further determine the role of SNCA in the development of PD, we screened a sample of 194 familial PD (FPD), 327 sporadic PD (SPD), and 215 controls with the Rep1 marker and 2 single nucleotide polymorphisms (SNPs) (770 and int4) in the SNCA gene.