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. 2023 May 31;7(1):469-473.
doi: 10.3233/ADR230023. eCollection 2023.

A Novel PSEN1 Variant Leading to Posterior Cortical Atrophy: A Case Report

Fausto Roveta  1 , Andrea Marcinnò  1 , Alberto Grassini  1 , Fabio Ferrandes  1 , Aurora Cermelli  1 , Silvia Boschi  1 , Salvatore Gallone  2 , Cristiana Atzori  3 , Daniele Imperiale  3 , Patrizia Dentelli  4   5 , Barbara Pasini  4   5 , Alfredo Brusco  4   5 , Elisa Rubino  1   2 , Innocenzo Rainero  1   2
Affiliations

A Novel PSEN1 Variant Leading to Posterior Cortical Atrophy: A Case Report

Fausto Roveta et al. J Alzheimers Dis Rep. .

Abstract

We describe a 52-year-old patient with a progressive visuospatial disorder and apraxia. Neuropsychological assessment, neuroradiological findings, and Alzheimer's disease (AD) core biomarker assay on cerebrospinal fluid led to a diagnosis of posterior cortical atrophy due to AD. We performed a next generation sequencing dementia-gene panel and found the c.1301 C>T p.(Ala434Val) variant in the Presenilin1 (PSEN1) gene. The missense change affects the PAL (Pro433-Ala434-Leu435) motif critical for catalytic activity of the macromolecular γ-secretase complex. Evolutionary and integrated bioinformatic tools predicted a deleterious effect of the variant supporting its role in the AD pathogenesis.

Keywords: Alzheimer’s disease; case reports; genetics; posterior cortical atrophy.

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Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
A) Patient’s family tree, with known cases of dementia blacked and deceased barred; the arrow points to the proband. B) Sanger sequencing confirmed the heterozygous c.1301 C>T variant.
Fig. 2
Fig. 2
Neuroimaging findings. From left to right: CT, FDG-PET, and Amyloid PET with flutemetamol of the patient consistent with the diagnosis of PCA due to AD.
See this image and copyright information in PMC

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