Mutations

PSEN1 E120G

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.25562A>G
Genomic Mutation Name (NT1): g.42116A>G
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: GAA to GGA

Findings

This mutation is associated with early-onset Alzheimer's disease in a Spanish kindred (Lladó et al., 2010; Gómez-Tortosa et al., 2010). This family was noted to have a particularly homogeneous age at onset (around 39 to 40 years), epileptic activity, and very rapid cognitive and functional deterioration.

The proband began to experience memory loss and progressive cognitive decline in his thirties. As the disease progressed, he developed seizures and difficulties with gait. He died at the age of 44. His father, paternal uncle, and sister were also affected. The father developed behavioral disturbances and memory deficits around age 39 and died at age 42. He had generalized seizures. His homozygous twin brother also developed symptoms in his late thirties and died at age 42. The proband’s sister began having recurrent generalized seizures at age 39. Memory deficits began simultaneously and progressed to substantial cognitive deterioration within two years. The mutation was shown to segregate with disease in this family (Gómez-Tortosa et al., 2010).

Neuropathology

Neuropathological examination of the proband’s brain revealed frequent amyloid plaques and neurofibrillary tangles along with severe amyloid angiopathy (Lladó et al., 2010).

Biological Effect

Unknown. In silico, this mutation has been predicted “probably damaging” by PolyPhen (Gómez-Tortosa et al., 2010).

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References

Paper Citations

  1. . [New mutation in the PSEN1 (E120G) gene associated with early onset Alzheimer's disease]. Neurologia. 2010 Jan-Feb;25(1):13-6. PubMed.
  2. . Clinical-genetic correlations in familial Alzheimer's disease caused by presenilin 1 mutations. J Alzheimers Dis. 2010;19(3):873-84. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . [New mutation in the PSEN1 (E120G) gene associated with early onset Alzheimer's disease]. Neurologia. 2010 Jan-Feb;25(1):13-6. PubMed.
  2. . 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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