Mutations

PSEN1 L113P

Overview

Pathogenicity: Frontotemporal Dementia : Pathogenic, Possible Alzheimer's Disease : Pathogenic
Clinical Phenotype: Frontotemporal Dementia
Reference Assembly: GRCh37 (105)
Position: Chr14:73637755 T>C
dbSNP ID: rs63751399
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTA to CCA
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This mutation was identified in a French family known as SAL 513. The reported pedigree consisted of six family members affected by early onset dementia across four generations. The inheritance pattern was consistent with autosomal-dominant inheritance. Ages of onset were 38, 39, 40, 45, and 50 years for the five family members for whom data was reported. The disease manifested with behavioral impairments, including impulsiveness and stereotyped behavior, as well as changes in mood and personality, and loss of personal and social awareness. Myoclonic jerks and seizures appeared later. Three affected members of the family fulfilled the Lund and Manchester criteria for frontotemporal dementia (Lund and Manchester Group, 1994) and consensus criteria for FTD (Neary et al., 1998). However, others have suggested the mutation may cause a frontal variant of AD, rather than FTD, since neuropathology includes plaques and tangles typical of AD (Bergmans and De Strooper, 2010, July 2012 webinar).

The mutation was detected in the two affected family members screened and absent in a healthy 67-year-old sister of the proband, supporting segregation of the mutation with disease (Raux et al., 2000).

Neuropathology

CT scans from two patients showed predominant frontotemporal atrophy and SPECT showed hypoperfusion including the frontal lobes (Raux et al., 2000). In addition, AD-like plaques and tangles were reported (Bergmans and De Strooper, 2010).

Biological Effect

Unknown.

Last Updated: 19 Feb 2019

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References

Webinar Citations

  1. Weeding Mendel’s Garden: Can We Hoe Dubious Genetic Associations?

Paper Citations

  1. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry. 1994 Apr;57(4):416-8. PubMed.
  2. . Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546-54. PubMed.
  3. . gamma-secretases: from cell biology to therapeutic strategies. Lancet Neurol. 2010 Feb;9(2):215-26. PubMed.
  4. . Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. 2000 Nov 28;55(10):1577-8. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. 2000 Nov 28;55(10):1577-8. PubMed.

Other mutations at this position

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