Mutations

PSEN1 F105C

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1):
Genomic Mutation Name (NT1):
dbSNP ID:
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: TTT to TGT

Findings

This mutation was identified in a family from mainland China with three affected individuals over two generations. Disease in this family was described as a relatively pure amnestic syndrome without atypical motor or behavioral features. The proband developed progressive memory deficits at age 45, with later behavioral changes. Her brother developed similar symptoms beginning at age 51. Their father died with unclassified severe dementia at age 60, with onset around age 50. The mutation appears to segregate with disease in this family; it was present in the proband and her affected brother, but absent in an unaffected family member (Jiao et al., 2014; Deng et al., 2014).

Previous studies had identified other pathogenic mutations at this position, which resulted in replacement of phenylalanine with isoleucine (F105I), valine (F105V) or leucine (F105L).

Neuropathology

Unknown. Neuroimaging of the two affected siblings showed atrophy in the hippocampus and frontotemporal regions and enlargement of ventricles (Deng et al., 2014).

Biological Effect

Unknown. Predicted "damaging" by in silico analysis with SIFT software and "definitely pathogenic" according to the proposed algorithm in Guerreiro et al., 2010 (Jiao et al., 2014; Deng et al., 2014).

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References

Mutations Citations

  1. PSEN1 F105I
  2. PSEN1 F105V
  3. PSEN1 F105L

Paper Citations

  1. . Mutational analysis in early-onset familial Alzheimer's disease in Mainland China. Neurobiol Aging. 2014 Aug;35(8):1957.e1-6. Epub 2014 Feb 20 PubMed.
  2. . Identification of a Novel Mutation in the Presenilin 1 Gene in a Chinese Alzheimer's Disease Family. Neurotox Res. 2014 Apr 16; 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.

Further Reading

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Primary Papers

  1. . Mutational analysis in early-onset familial Alzheimer's disease in Mainland China. Neurobiol Aging. 2014 Aug;35(8):1957.e1-6. Epub 2014 Feb 20 PubMed.
  2. . Identification of a Novel Mutation in the Presenilin 1 Gene in a Chinese Alzheimer's Disease Family. Neurotox Res. 2014 Apr 16; PubMed.

Other mutations at this position

View Table