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 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.
Farrer
M
M
Neurogenetics Laboratory, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
Destée
A
A
Levecque
C
C
Singleton
A
A
Engelender
S
S
Becquet
E
E
Mouroux
V
V
Richard
F
F
Defebvre
L
L
Crook
R
R
Hernandez
D
D
Ross
C A
CA
Hardy
J
J
Amouyel
P
P
Chartier-Harlin
M C
MC
D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010375:Pedigree
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human