Mutations

PSEN1 L85P

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease, Spastic Paraparesis
Genomic Mutation Name (MET1): g.22939T>C
Genomic Mutation Name (NT1): g.39493T>C
dbSNP ID: rs63750599
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: CTC to CCC

Findings

This missense mutation in exon 4 was first identified in a young Japanese man living in the United States. While a college student in his early 20s, the proband developed early onset dementia with spastic paraparesis. Sequence analysis revealed a PSEN1 mutation; no other mutations in the coding regions of PSEN1, PSEN2, or APP were detected. The patient’s parents and two siblings did not carry the L85P mutation or any other mutation in PSEN1, PSEN2, or APP. The fact that neither parent was a mutation carrier suggests that it may be a rare de novo mutation. In addition to progressive impairment of intelligence and memory, neuropsychological evaluation of the patient revealed a complex visual problem not attributable to abnormalities of optic fundi, visual acuity, visual field, or color identification. Thus, the patient was thought to have a visual variant of AD (see Levine et al., 1993) rather than typical AD (Ataka et al., 2004).

Neuropathology

Neuropathological examination was not available. Single-photon emission computed tomography (SPECT) and PET showed bilateral hypoperfusion and hypometabolism in the occipital and temporal lobes (Ataka et al., 2004).

Biological Effect

The mutation was associated with a marked increase in Aβ42 production and in the Aβ42/Aβ40 ratio, supporting pathogenicity (Ataka et al., 2004).

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References

Paper Citations

  1. . The visual variant of Alzheimer's disease: a clinicopathologic case study. Neurology. 1993 Feb;43(2):305-13. PubMed.
  2. . A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis. Arch Neurol. 2004 Nov;61(11):1773-6. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis. Arch Neurol. 2004 Nov;61(11):1773-6. PubMed.