Mutations

PSEN1 T116I

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.25550C>T
Genomic Mutation Name (NT1): g.42104C>T
dbSNP ID: rs63750730
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: ACC to ATC

Findings

This mutation was first reported in a 48-year-old Italian woman with a three-year history of progressive memory impairment. She did not have a family history of dementia, so the mutation may have arisen de novo; however, it may have been transmitted through the maternal line. The proband’s mother and maternal grandmother died in their 40s from unrelated causes (bone cancer and an accident, respectively), so it is not known whether they would have developed dementia had they lived. The mutation was absent in the patient’s father and in 100 healthy unrelated controls (La Bella et al., 2004).

This mutation was also detected in the proband of a family known as ANG 008, in which four family members were also affected by dementia. This study reported the age of onset as 40 to 47 years. Family members met NINCDS-ADRDA criteria for Alzheimer’s disease, but postmortem confirmation of the diagnosis was not available (Raux et al., 2005). This family was also described in a large French study. The clinical data for five affected family members was summarized as disease onset at age 38 to 44 (younger than previously reported), and duration ranging from three to five years. DNA from family members was not available, therefore segregation with disease could not be determined.

Neuropathology

Unknown.

Biological Effect

Unknown. The T116I mutation has been classified as definitely pathogenic according to the algorithm proposed by Guerreiro et al., 2010 (Wallon et al., 2012).

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References

Paper Citations

  1. . A novel mutation (Thr116Ile) in the presenilin 1 gene in a patient with early-onset Alzheimer's disease. Eur J Neurol. 2004 Aug;11(8):521-4. PubMed.
  2. . Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005 Oct;42(10):793-5. Epub 2005 Jul 20 PubMed.
  3. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.
  4. . The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers. J Alzheimers Dis. 2012 Jan 1;30(4):847-56. PubMed.

External Citations

  1. .

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A novel mutation (Thr116Ile) in the presenilin 1 gene in a patient with early-onset Alzheimer's disease. Eur J Neurol. 2004 Aug;11(8):521-4. PubMed.

Other mutations at this position

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