Mutations

PSEN1 M233I

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.44718G>C
Genomic Mutation Name (NT1): g.61324G>C
dbSNP ID: rs63751479
Coding/Non-Coding: Coding
Genomic Region: Exon 7
Mutation Type: Point, Missense
Codon Change: ATG to ATC

Findings

This mutation, detected in a patient with neuropathogically confirmed Alzheimer's disease, is predicted to result in the substitution of isoleucine for methionine. At age 28, the patient began to experience memory problems which affected activities of daily living. Her disease progressed quickly, with worsening memory and language impairments and stereotyped and perseverative behavior. By age 31, pyramidal signs were present, associated with a cerebellar syndrome, rigidity, and myoclonic jerking. She continued to deteriorate, becoming immobile, incontinent, and mute, with swallowing difficulties and generalized tonic-clonic seizures. She died at age 36.

The parents of the proband were unaffected and did not carry the mutation. Paternity was confirmed by microsatellite typing, therefore the mutation is thought to have arisen de novo in the proband. The mutation was absent in 50 unrelated control subjects (Portet et al., 2003).

Neuropathology

A right frontal brain biopsy showed pathology consistent with a diagnosis of AD, including amyloid plaques and tau-positive neurofibrillary tangles. Astrocytic gliosis, spongiosis, prion protein, and inflammatory signs were not observed.

Biological Effect

Unknown.

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References

Paper Citations

  1. . Very early onset AD with a de novo mutation in the presenilin 1 gene (Met 233 Leu). Neurology. 2003 Oct 28;61(8):1136-7. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Very early onset AD with a de novo mutation in the presenilin 1 gene (Met 233 Leu). Neurology. 2003 Oct 28;61(8):1136-7. PubMed.

Other mutations at this position

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