Mutations

PSEN1 F105V

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.22998T>G
Genomic Mutation Name (NT1): g.39552T>G
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: TTT to GTT

Findings

This mutation was reported in a Spanish patient who met clinical criteria for Alzheimer’s disease (Gómez-Tortosa et al., 2010). The patient began to experience memory problems at age 52. The patient did not have a known family history of dementia and segregation with disease could not be established because the patient’s only brother was cognitively healthy at age 55 and both parents had died at a young age. Her cognitive decline was described as fairly typical for AD, with no significant motor or atypical features. The mutation was presumed pathogenic based on three lines of evidence, including the patient’s relatively early age at onset, in silico analysis that predicted the mutation to be “probably damaging”, and the existence of two known pathogenic mutations at this codon, F105L (Finckh et al., 2000) and F105I (Raux et al., 2005).

Neuropathology

Unknown.

Biological Effect

Unknown. Predicted to be probably damaging by in silico analysis using PolyPhen (Gómez-Tortosa et al., 2010).

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References

Paper Citations

  1. . Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-84. PubMed.
  2. . High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. PubMed.
  3. . Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005 Oct;42(10):793-5. Epub 2005 Jul 20 PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-84. PubMed.

Other mutations at this position

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