Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

@article{Polymeropoulos1997MutationIT,
  title={Mutation in the $\alpha$-Synuclein Gene Identified in Families with Parkinson's Disease},
  author={M. Polymeropoulos and C. Lavedan and E. Leroy and S. Ide and A. Dehejia and A. Dutra and B. Pike and H. Root and J. Rubenstein and R. Boyer and E. Stenroos and S. Chandrasekharappa and A. Athanassiadou and T. Papapetropoulos and W. Johnson and A. Lazzarini and R. Duvoisin and G. Iorio and L. Golbe and R. Nussbaum},
  journal={Science},
  year={1997},
  volume={276},
  pages={2045-2047}
}
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three… Expand
No pathogenic mutations in the β-synuclein gene in Parkinson's disease
TLDR
11 families consistent with autosomal dominant inheritance of probable Parkinson's disease (PD) are presented, and Sequencing the translated exons of the β-synuclein gene failed to identify any pathogenic mutation. Expand
Point Mutations in the α-Synuclein Gene.
TLDR
It was concluded that this mutation is the cause of PD in this family, and the first report of a mutation causing clinically and pathologically defined idiopathic PD associated with the critical pathologic finding, the intraneuronal inclusions in brainstem nuclei including the substantia nigra. Expand
The role of the α-synuclein gene mutation in patients with sporadic Parkinson’s disease in the United Kingdom
TLDR
DNA from 70 patients with Parkinson's disease was screened for the G209A mutation, suggesting that it is not relevant for most patients with sporadic idiopathic Parkinson’s disease. Expand
Low frequency of α‐synuclein mutations in familial Parkinson's disease
TLDR
Primers and methods for exonic sequencing of this gene were developed and the entire coding region of the gene was sequenced and no genetic variation was found, suggesting that NACP is not the chromosome 4 locus for disease. Expand
Absence of mutations in the coding region of the α-synuclein gene in pathologically proven Parkinson's disease
TLDR
Using reverse transcribed-polymerase chain reaction (RT-PCR) technique, the entire coding region of the α-synuclein gene is sequenced using brain tissue from 24 pathologically proven Parkinson's disease cases, suggesting that a mutation at the coding region is unlikely to be responsible for nigrostriatal degeneration in typical sporadic Parkinson's Disease. Expand
Causal relation between α-synuclein locus duplication as a cause of familial Parkinson's disease
TLDR
The results indicate that SNCA is more frequently associated with familial Parkinson's disease than previously thought, and that there is a clear dosage effect according to the number of supernumerary copies of this gene. Expand
Sequencing of the α-Synuclein Gene in a Large Series of Cases of Familial Parkinson's Disease Fails to Reveal any Further Mutations
TLDR
It is concluded that the A53T change described in the alpha-synuclein gene is a rare cause of PD or may even be a rare variant. Expand
Evaluation of the γ-synuclein gene in German Parkinson's disease patients
TLDR
The results do not support a major role of the γ-synuclein gene in Parkinson's disease and no evidence for an increased risk of combined genotypes of polymorphisms in theγ- synuclein and the α-syn nuclein gene was found. Expand
Genetic dissection of familial Parkinson's disease.
TLDR
The elucidation of polygenic changes in the dopamine pathway, mitochondrial dysfunction, and metabolism of xenobiotics is now technically possible by means of association and genotype studies and will have important implications for the development of individual therapeutic strategies to prevent disease progression. Expand
Genetic Analysis of Synphilin-1 in Familial Parkinson's Disease
TLDR
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, but subsequent haplotype, sequencing, and association analyses suggest that variability within the locus does not confer susceptibility to Parkinson's Disease. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 18 REFERENCES
Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmedExpand
A familial Alzheimer's disease locus on chromosome 1
TLDR
A 112-base pair allele of D1S479 co-segregated with the disease in five of seven families, which is consistent with a common genetic founder. Expand
A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene
TLDR
The intron/exon structure of the PS-1 gene has been determined and this information has been used to identify a mutation in the splice acceptor site for exon 9 in a family with early onset Alzheimer's disease. Expand
The human NACP/alpha-synuclein gene: chromosome assignment to 4q21.3-q22 and TaqI RFLP analysis.
TLDR
The chromosome localization of the NACP gene was determined using PCR and Southern blotting analyses of somatic cell hybrids and in situ chromosome hybridization, and a two-allele RFLP was identified by screening genomic DNA from unrelated Caucasian individuals by using Southern blot analysis. Expand
Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene
TLDR
Analysis of the nucleotide sequence of the open reading frame of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (50–70 years versus 30–60 years for AD3). Expand
A large kindred with autosomal dominant Parkinson's disease
TLDR
It is concluded that what is probably a single gene without an additional environmental insult can cause the pathological changes typical of PD and will enhance the likelihood of significant genetic component in the cause of sporadic PD. Expand
Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome
TLDR
It is shown here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrPcodon 102 may lead to the development of Gerstmann–Sträussler syndrome. Expand
High-resolution mapping of SNCA encoding α-synuclein, the non-Aβ component of Alzheimer’s disease amyloid precursor, to human chromosome 4q21.3→q22 by fluorescence in situ hybridization
The human α-synuclein gene (SNCA) was previously identified as the non-Aβ component of Alzheimer’s disease amyloid precursor (NACP). A cosmid clone containing this gene has been isolated and mapped by
A clinical genetic study of Parkinson's disease
TLDR
The cumulative risk of Parkinson's disease in relatives of patients seen consecutively for 1 year and the proportion of secondary cases of PD as a function of pedigree completeness was assessed, suggesting significant familial aggregation in a subset of randomly ascertained families. Expand
The anterior olfactory nucleus in Parkinson's disease
TLDR
It is shown that the presence of Lewy bodies in the olfactory bulb and tract is associated with significant neuronal loss in patients with idiopathic Parkinson's disease. Expand
...
1
2
...