Genetic analysis of synphilin-1 in familial Parkinson's disease

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 vifro. 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. (C) 2001 Academic Press.