Genetic analysis of synphilin-1 in familial Parkinson's disease.
Farrer M., Destée A., Levecque C., Singleton A., Engelender S., Becquet E., Mouroux V., Richard F., Defebvre L., Crook R., Hernandez D., Ross CA., Hardy J., Amouyel P., Chartier-Harlin MC.
alpha-Synuclein is present in Lewy bodies of patients with both sporadic and familial Parkinson's disease. However, pathogenic mutations Ala30Pro and Ala53Thr in alpha-synuclein are rare causes of disease. Synphilin-1 has been demonstrated to associate with alpha-synuclein and promote the formation of cytosolic inclusions in vitro. Two-point genetic linkage analysis of a dinucleotide repeat within the synphilin-1 gene initially implicated this locus as a cause of Parkinson's disease in three of nine families. However, subsequent haplotype, sequencing, and association analyses in these three families and an independent case-control series suggest that variability within the locus does not confer susceptibility to Parkinson's disease.