PSEN1 M233L (A>C)


Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73659500 A>C
dbSNP ID: rs63751287
Coding/Non-Coding: Coding
Genomic Region: Exon 7
Mutation Type: Point, Missense
Codon Change: ATG to CTG


This mutation was first detected in an individual from Spain who met NINCDS-ADRDA criteria for Alzheimer’s disease (McKhann et al., 1984). Symptom onset occurred at age 46; further clinical details were not reported. The patient did not have a family history of dementia, and segregation with disease could not be assessed (Aldudo et al., 1999).

This mutation was subsequently found in another individual. Clinical details were not reported (Rogaeva et al., 2001).

More recently, this mutation was found in a Han Chinese family with a history of early-onset AD (Jiang et al., 2014). The reported pedigree shows five affected individuals over two generations: four siblings and their mother. The proband was a 38-year-old woman with a one-year-history of memory loss. Disease in this family was characterized by early onset and rapid progression, with onset ranging from 37 to 44 years of age. Epilepsy was also common, as was paralysis and psychiatric symptoms. The mutation appeared to segregate with disease in this family: It was detected in two affected individuals but absent in the proband’s father who was unaffected at age 76.


Unknown. Imaging showed global cerebral atrophy (Jiang et al., 2014).

Biological Effect

Factors in support of pathogenicity include the fact that other pathogenic mutations have been described at codon 233, and a pathogenic mutation (M239V), has been documented at the homologous codon in PSEN2.


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Mutations Citations

  1. PSEN2 M239V

Paper Citations

  1. . Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. PubMed.
  2. . DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations. Hum Mutat. 1999;14(5):433-9. PubMed.
  3. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.
  4. . Identification of PSEN1 mutations p.M233L and p.R352C in Han Chinese families with early-onset familial Alzheimer's disease. Neurobiol Aging. 2015 Mar;36(3):1602.e3-6. Epub 2014 Dec 18 PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database