Analysis of the coding and the 5' flanking regions of the alpha-synuclein gene in patients with Parkinson's disease.

Missense mutations of the alpha-synuclein gene have been reported to explain a few kindreds with autosomal dominant Parkinson's disease (PD). In order to identify mutations in our PD patients, we have screened the coding region and 5'flanking region of the gene. DNA samples from 50 patients with familial PD were screened via single-strand conformation polymorphism (SSCP) for mutations in the alpha-synuclein gene. The 5' flanking region was examined in 117 additional PD patients (27 patients with unclear family history for PD, and 90 patients without family history) and in 169 control subjects. We found one change (G199A) in exon 4 in one family with a pattern of autosomal dominant PD. However, this mutation did not result in an amino acid substitution (valine) and did not segregate completely with PD. The analysis of the 5' flanking region also showed a new polymorphism, a nucleotide insertion (- 164insA) linked to a nucleotide substitution (C-116G), in patients and in controls. The -164insA/C-116G allele was present in 52.3% of the patients and in 47.6% of the controls. We did not find significant differences regarding the allelic and genotype frequencies between PD and control groups. These results suggest that mutations in the alpha-synuclein gene are a very rare cause of familial PD and that the novel -164insA/C-116G polymorphism in the 5' flanking region does not confer susceptibility to develop PD. Copyright 2001 Movement Disorder Society.