Mutations

PSEN1 L173F G>C

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genome Build: 105
Position: Chr14:73653599 G>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Genomic Region: Exon 6
Mutation Type: Point, Missense
Codon Change: TTG to TTC

Findings

This mutation was detected in two siblings from a family affected by early onset Alzheimer's disease (Kasuga et al., 2009). The reported pedigree shows six affected individuals over three generations. The proband and her affected sister were heterozygous carriers, suggesting segregation with disease. In this family, depression and psychiatric symptoms preceded cognitive decline. The proband was treated for depression at age 29. By age 48 she had developed personality changes and visual and auditory hallucinations. She also developed parkinsonian symptoms, including rigidity and postural instability. Her sister experienced a similar disease course, starting with depression and bipolar symptoms as an adolescent. By age 40 she had developed cognitive decline as well as parkinsonism. The mutation was absent in 110 controls.

Neuropathology

Unknown. MRI in both sisters showed atrophy of the medial temporal lobe. SPECT showed hypoperfusion of the posterior cingulate gyri and other cortical areas.

Biological Effect

N2a cells transfected with mutant PSEN1 secreted significantly more Aβ42 than cells expressing wild-type PSEN1. The Aβ42:Aβ40 ratio was also increased.

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References

Paper Citations

  1. . Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation. J Neurol. 2009 Aug;256(8):1351-3. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Depression and psychiatric symptoms preceding onset of dementia in a family with early-onset Alzheimer disease with a novel PSEN1 mutation. J Neurol. 2009 Aug;256(8):1351-3. PubMed.

Other mutations at this position

Alzpedia