Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
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 emerging at age 4 in a 32-year-old carrier in the next generation of the same family (Fray et al., 2020). This patient had memory and attention deficits, as well as depression. Of note, except for this individual, epilepsy was not observed in any other family member.

Neuropathology

Unknown. In one case, MRI showed bilateral atrophy, especially in the parietal and temporal lobes (Fray et al., 2015). In the patient with epilepsy, brain MRI at the age of 31 showed cortical atrophy predominant in the frontal and temporal regions without obvious epileptogenic lesions (Fray et al., 2020).

Biological Effect

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

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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 Jun;26(3):167-170. Epub 2020 Apr 3 PubMed.

Further Reading

No Available Further Reading