一名散发性早发性阿尔茨海默病伴显著小脑共济失调患者中的一种新型PSEN1突变。

A novel PSEN1 mutation in a patient with sporadic early-onset Alzheimer's disease and prominent cerebellar ataxia.

作者信息

Testi Silvia, Peluso Silvio, Fabrizi Gian Maria, Antenora Antonella, Russo Cinzia Valeria, Pappatà Sabina, Padovani Alessandro, Ferrarini Moreno, Filla Alessandro

机构信息

Department of Neurological and Movement Sciences, Section of Neuropathology, University of Verona, Italy.

Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

出版信息

J Alzheimers Dis. 2014;41(3):709-14. doi: 10.3233/JAD-140081.

DOI:10.3233/JAD-140081

PMID:24718101

Abstract

PSEN1 gene mutations represent the first cause of familiar early-onset Alzheimer's disease (EOAD). More than 190 mutations in PSEN1 have been reported to date. The clinical phenotype is mainly characterized by cognitive decline but movement disorders have been rarely described. We report a novel PSEN1 mutation (p.Thr147Pro) responsible for a sporadic early-onset dementia with prominent cerebellar symptoms, resembling a spinocerebellar syndrome. Neuroradiological and cerebrospinal fluid biomarkers examinations were performed on the patient, showing typical findings of EOAD and suggesting the pathogenicity of the novel mutation. Our study widens the number of unusual phenotypes related to PSEN1 mutations.

摘要

早老素1（PSEN1）基因突变是家族性早发型阿尔茨海默病（EOAD）的首要病因。迄今为止，已报道了190多种PSEN1基因突变。其临床表型主要以认知功能减退为特征，但运动障碍鲜有描述。我们报告了一种新的PSEN1基因突变（p.Thr147Pro），该突变导致了一例散发的早发型痴呆，伴有明显的小脑症状，类似脊髓小脑综合征。对该患者进行了神经放射学和脑脊液生物标志物检查，结果显示为EOAD的典型表现，并提示该新突变具有致病性。我们的研究扩大了与PSEN1基因突变相关的异常表型的范围。