Mutations

PSEN1 L166V

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 6
Mutation Type: Point, Missense
Codon Change: CTT to GTT

Findings

This mutation was one of several rare variants detected by exome sequencing in a British cohort composed of 47 early onset Alzheimer’s disease cases and 179 elderly controls who were free of AD neuropathology. The mutation was detected in one individual with AD and was absent in all controls. The mutation carrier, who was Caucasian, did not a have a family history of dementia, suggesting a possible de novo mutation. The patient presented with symptoms typical of AD as well as extrapyramidal signs, including parkinsonism and myoclonus. His symptoms began at age 42 with increasing memory trouble that interfered with his ability to work. Verbal expression, reading and mathematical skills, and spatial orientation were also affected. The patient died at age 50, eight years after symptom onset (Sassi et al., 2014).

Neuropathology

SPECT imaging performed four years after symptom onset showed temporoparietal hypoperfusion. Postmortem evaluation revealed neuropathology consistent with AD, including advanced plaques and tangles (CERAD C, Braak stage VI).

Biological Effect

Unknown. This mutation is predicted to be possibly damaging in silico by SIFT and PolyPhen-2, and it has probable pathogenicity according to the algorithm proposed by Guerreiro et al., 2010.

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References

Paper Citations

  1. . Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging. 2014 Oct;35(10):2422.e13-6. Epub 2014 May 2 PubMed.
  2. . 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. . Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging. 2014 Oct;35(10):2422.e13-6. Epub 2014 May 2 PubMed.

Other mutations at this position

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