Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr14:73637665 T>C
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ATC to ACC
Reference Isoform: PSEN1 isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This mutation was identified in two Tunisian siblings affected by early onset Alzheimer’s disease (Achouri-Rassas et al., 2015). The reported pedigree shows 10 affected individuals over three generations. The siblings, a brother and sister, were diagnosed with AD at the ages of 55 and 64, respectively, meeting NINCDS-ADRDA criteria for probable AD. The siblings presented with prominent behavioral symptoms, along with depression, irritability, and visual hallucinations (Fray et al., 2015). Segregation with disease could not be assessed due to lack of DNA from family members.

A subsequent publication reported refractory epilepsy developing prior to cognitive decline in a 32-year-old Tunisian carrier with a family history of early onset AD (Fray et al., 2020).

Neuropathology

Unknown. MRI showed bilateral atrophy, especially in the parietal and temporal lobes (Fray et al., 2015).

Biological Effect

Unknown. In silico, this mutation is predicted to be probably damaging by PolyPhen2.

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

1. Achouri-Rassas A, Ben Ali N, Fray S, Hadj Fredj S, Kechaou M, Zakraoui NO, Cherif A, Chabbi S, Anane N, Messaoud T, Gouider R, Belal S. Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset Alzheimer's disease. Neurobiol Aging. 2015 Oct;36(10):2904.e9-11. Epub 2015 Jun 12 PubMed.
2. Fray S, Ali NB, Rassas AA, Kechaou M, Oudiaa N, Cherif A, Echebbi S, Messaoud T, Belal S. Early psychiatrics symptoms in familial Alzheimer's disease with presenilin 1 mutation (I83T). J Neural Transm (Vienna). 2016 Apr;123(4):451-3. Epub 2015 Dec 22 PubMed.
3. Fray S, Rassas A, Messaoud T, Belal S. Refractory epilepsy in PSEN 1 mutation (I83T). Neurocase. 2020 Apr 3;:1-4. PubMed.

Further Reading

No Available Further Reading