一种导致后皮质萎缩的新型变异：病例报告

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

作者信息

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

机构信息

Aging Brain and Memory Clinic, Department of Neuroscience, University of Torino, Torino, Italy.

Department of Neuroscience and Mental Health, Città della Salute e della Scienza University Hospital, Torino, Italy.

出版信息

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

DOI:10.3233/ADR230023

PMID:37313494

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10259045/

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 ( gene. The missense change affects the PAL (Pro433-Ala434-Leu435) motif critical for catalytic activity of the macromolecular -secretase complex. Evolutionary and integrated bioinformatic tools predicted a deleterious effect of the variant supporting its role in the AD pathogenesis.

摘要

我们描述了一位患有进行性视觉空间障碍和失用症的52岁患者。神经心理学评估、神经影像学检查结果以及脑脊液中的阿尔茨海默病（AD）核心生物标志物检测，最终诊断为AD所致的后部皮质萎缩。我们进行了下一代测序痴呆症基因检测，在早老素1（PSEN1）基因中发现了c.1301C>T p.(Ala434Val)变异。该错义变化影响了对大分子γ-分泌酶复合物催化活性至关重要的PAL（Pro433-Ala434-Leu435）基序。进化和综合生物信息学工具预测该变异具有有害作用，支持其在AD发病机制中的作用。