A novel presenilin 2 gene mutation (D439A) in a patient with early-onset Alzheimer’s disease

@article{Lle2001ANP,
  title={A novel presenilin 2 gene mutation (D439A) in a patient with early-onset Alzheimer’s disease},
  author={A. Lle{\'o} and Rafael Blesa and Jordi Gendre and Magdalena Castellv{\'i} and Pau P{\'a}stor and Rosa Queralt and Rafael Oliva},
  journal={Neurology},
  year={2001},
  volume={57},
  pages={1926 - 1928}
}
The authors describe a novel missense mutation in the presenilin 2 (PSEN2) gene at residue 439 that predicts an aspartate-to-alanine substitution (D439A). This mutation was found in a 58-year old patient who displayed a progressive dementia at the age of 52. The mutation was absent in his cognitively normal relatives. Haplotype analysis indicated that his affected mother was the most probable mutation carrier. The D439A mutation is located near the C-terminal end of the PS2 protein, a region… Expand
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References

SHOWING 1-10 OF 13 REFERENCES
A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease
TLDR
The first mutation in a presenilin gene in a Spanish AD case is reported, which is the third mutation detected for the PS-2 gene. Expand
Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease.
TLDR
A systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases found polymorphisms were detected in the promoter and the 5'- non-Coding region of PS-1 and in intronic and exonic sequences of PS -- that will be useful in genetic association studies. Expand
Candidate gene for the chromosome 1 familial Alzheimer's disease locus
TLDR
The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic. 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
High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.
TLDR
It is concluded that because of the lack of specific antemortem diagnostic markers for FAD and hereditary prion disease, all four genes should be included in a molecular diagnostic program in patients with EOD who had PFH. Expand
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
TLDR
It is demonstrated that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene that causes an amino-acid substitution close to the carboxy terminus of the β-amyloid peptide. Expand
Wide range in age of onset for chromosome 1‐related familial Alzheimer's disease
TLDR
It is concluded that, unlike the chromosome 14 gene, mutations in the chromosome 1 FAD gene may result in individuals with a late age of onset overlapping with the more common sporadic form of the disease occurring in the general population. Expand
Mutational Analysis of Intrinsic Regions of Presenilin 2 That Determine Its Endoproteolytic Cleavage and Pathological Function*
TLDR
The data suggest that the determinants of the PS2 cleavage site reside within a large region and that the pathological function of PS2 is exerted by familial Alzheimer's disease mutations not related to the cleavage of holoproteins. Expand
The molecular and genetic basis of AD: The end of the beginning
TLDR
It is clear that early onset autosomal dominant AD is a heterogeneous set of disorders caused in separate families by different genetic mutations, and only one-third of identical twins are concordant for AD, indicating that nongenetic—perhaps environmental—factors are important in the pathogenesis of AD. Expand
Evidence That Levels of Presenilins (PS1 and PS2) Are Coordinately Regulated by Competition for Limiting Cellular Factors*
TLDR
It is revealed that compromised accumulation of murine PS1 and PS2 derivatives resulting from overexpression of human PS1 occurs in a manner independent of endoproteolytic cleavage, consistent with a model in which the abundance of PS2 fragments is regulated coordinately by competition for limiting cellular factor(s). Expand
...
1
2
...