Mutations

PSEN1 T116N

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.25550C>A
Genomic Mutation Name (NT1): g.42104C>A
dbSNP ID: rs63750730
Coding/Non-Coding: Coding
Genomic Region: Exon 5
Mutation Type: Point, Missense
Codon Change: ACC to AAC

Findings

This mutation was first reported in a Danish family with four affected individuals over three generations. The mutation was observed to segregate with early onset Alzheimer’s disease in an autosomal dominant manner. Age at onset in the four known affected individuals ranged from 35 to 41 years (mean: 38 years). Progression was rapid in this family, with duration from symptom onset to death averaging 5.7 years (range: four to eight years). The clinical diagnosis of AD was confirmed at autopsy in one family member (Romero et al., 1999).

The T116N mutation was detected in a second kindred with four affected family members. The age of onset in this family, known as ALZ 157, ranged from 30 to 33 years (Raux et al., 2005). It was also found in two additional unrelated patients with AD. One experienced symptom onset at age 37 (Guerreiro et al, 2010). Clinical details were not available in the other patient (Rogaeva et al., 2001).

Neuropathology

Neuropathology consistent with a diagnosis of AD was found in one mutation carrier (Romero et al., 1999).

Biological Effect

Unknown.

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References

Paper Citations

  1. . A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease. Neuroreport. 1999 Aug 2;10(11):2255-60. 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. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease. Neuroreport. 1999 Aug 2;10(11):2255-60. PubMed.

Other mutations at this position

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