Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease, Myoclonic seizure
Reference Assembly: GRCh37 (105)
Position: Chr14:73653585 T>C
dbSNP ID: rs63750418
Coding/Non-Coding: Coding
Genomic Region: Exon 6
Mutation Type: Point, Missense
Codon Change: TCA to CCA


This mutation was reported in a Spanish family with four affected members over two generations, a mother and three of her children (Ezquerra et al., 1999). The clinical phenotype in this family included myoclonus in addition to early onset dementia. The proband developed symptoms at the age of 31, starting with irritability, personality changes, and memory impairment.

Three of the proband’s offspring subsequently developed early onset AD, with a homogeneous age of onset (33, 34, and 35 years). Two of the siblings also had myoclonic jerks. Two affected individuals were genetically tested and found to carry the mutation, but segregation with disease could not be formally shown due to lack of available DNA from additional family members. The mutation was not detected in 100 controls from the general population or among 50 unrelated sporadic AD patients from Spain.


Cerebral biopsy of the proband revealed numerous plaques and neurofibrillary tangles, neurite irregularities, neuronal lipofuscin, and mild astrocytosis, overall consistent with a diagnosis of Alzheimer’s disease (Ezquerra et al., 1999).

Biological Effect



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Paper Citations

  1. . A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures. Neurology. 1999 Feb;52(3):566-70. PubMed.

Further Reading


  1. . Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol. 2002 Nov;59(11):1759-63. PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

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Primary Papers

  1. . A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures. Neurology. 1999 Feb;52(3):566-70. PubMed.

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