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

Missense mutations of the alpha -synuclein gene have been reported to expla in a few kindreds with autosomal dominant Parkinson's disease (PD). In orde r to identify mutations in our PD patients, we have screened the coding reg ion and 5' flanking region of the gene. DNA samples from 50 patients with f amilial PD were screened via single-strand conformation polymorphism for mu tations in the a-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 domi nant PD. However, this mutation did not result in an amino acid substitutio n (valine) and did not segregate completely with PD. The analysis of the 5' flanking region also showed a new polymorphism, a nucleotide insertion (-1 64insA) linked to a nucleotide substitution (C-116G), in patients and in co ntrols. 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 regardin g the allelic and genotype frequencies between PD and control groups. These results suggest that mutations in the alpha -synuclein gene are a very rar e cause of familial PD and that the novel -164insA/ C-116G polymorphism in the 5' flanking region does not confer susceptibility to develop PD. (C) 20 01 Movement Disorder Society.