A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures

Abstract

The absence of the PS1 Ser169Pro mutation in the general population and in sporadic AD cases together with its detection in the affected members of this kindred suggests that it is a pathogenic mutation. The serine to proline change predicts a kink in the alpha-helix of the transmembrane domain of the PS1 protein that could radically disrupt its normal structure. Further characterization of the effect of this mutation could help identify the function of the PS1 protein and the pathogenic mechanisms of AD.

Frequency of Mutations in the Presenilin and Amyloid Precursor Protein Genes in Early-Onset Alzheimer Disease in Spain

“…The H163R mutation had been previously described in several families with early-onset AD. 7,13 We found several nonpathogenic polymorphisms in the PSEN1 and PSEN2 (Table 3) genes. Most families presented a typical clinical picture, although some mutations were associated with a particular phenotype.…”

“…Most families presented a typical clinical picture, although some mutations were associated with a particular phenotype. The family carrying the V89L mutation in the PSEN1 gene 15 presented early behavioral disturbances and the families carrying the H163R and S169P 13 mutations showed early myoclonus and generalized tonic-clonic seizures.…”

Epilepsy and Dementia in the Elderly

“…Independent predictors of unprovoked seizures were younger age, African-American ethnic background, severer dementia and focal epileptiform activity on EEG. Considering patient age at onset, seizures are more likely to occur with early-onset disease, particularly in the familial form with the presenilin 1 mutation [41][42][43] .…”

A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances

“…Model building and analysis were performed in a Silicon Graphics Power Indigo 2 workstation using the molecular modelling package Insight II, Homology and Discover (Biosym -MSI, San Diego, CA, USA) as previously described. 10 …”