title: Low frequency of alpha-synuclein mutations in familial Parkinson's disease.
abstract: A mutation in exon 4 of the alpha-synuclein (NACP) gene has been reported to explain the chromosome 4 linkage to autosomal dominant Parkinson's disease. We developed primers and methods for exonic sequencing of this gene and sequenced the entire coding region of the gene in 6 families with autosomal dominant disease and in 2 cases of lytico and bodig from Guam. In addition, we have sequenced exon 4 of this gene in 5 cases of familial disease and have screened for the specific mutation (A53T) in a 40 cases of idiopathic Parkinson's disease, 3 cases of multisystem atrophy, and 15 cases of Lewy body dementia. We have found no genetic variation in the gene. We discuss these findings with respect to both the epidemiology of Parkinson's disease and the possibility that NACP is not the chromosome 4 locus for disease.
authors.affiliation: Mayo Clinic Jacksonville, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Farrer
authors.forename: F
authors.initials: F
authors.lastname: Wavrant-De Vrieze
authors.forename: R
authors.initials: R
authors.lastname: Crook
authors.forename: L
authors.initials: L
authors.lastname: Boles
authors.forename: J
authors.initials: J
authors.lastname: Perez-Tur
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: W G
authors.initials: WG
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Steele
authors.forename: D
authors.initials: D
authors.lastname: Maraganore
authors.forename: K
authors.initials: K
authors.lastname: Gwinn
authors.forename: T
authors.initials: T
authors.lastname: Lynch
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010302:Parkinson Disease, Secondary / Q000235:genetics; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein