早发性痴呆伴严重语言障碍中的一种新型早老素2突变（V393M）

A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment.

作者信息

Lindquist S G, Hasholt L, Bahl J M C, Heegaard N H H, Andersen B B, Nørremølle A, Stokholm J, Schwartz M, Batbayli M, Laursen H, Pardossi-Piquard R, Chen F, St George-Hyslop P, Waldemar G, Nielsen J E

机构信息

Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

出版信息

Eur J Neurol. 2008 Oct;15(10):1135-9. doi: 10.1111/j.1468-1331.2008.02256.x. Epub 2008 Aug 22.

DOI:10.1111/j.1468-1331.2008.02256.x

PMID:18727676

Abstract

BACKGROUND

Mutations in the Presenilin 2 gene (PSEN2) are rare causes of Alzheimer's disease (AD). Pathogenic mutations in the genes associated with autosomal dominant inherited AD have been shown to alter processing of the amyloid precursor protein (APP) resulting in a relative increase of the amount of Abeta42 peptide.

METHODS AND RESULTS

We present a patient with neuropathologically confirmed early-onset AD characterized by profound language impairment. The patient was heterozygous for a novel missense mutation in exon 11 of the PSEN2 gene leading to a predicted amino acid substitution from valine to methionine in position 393, a conserved residue. However, in vitro expression of PSEN2 V393M cDNA did not result in detectable increase of the secreted Abeta42/40 peptide ratio. The mutation was not found in 384 control individuals tested.

CONCLUSIONS

The possible pathogenic nature of the mutation is not clarified. We discuss the limitations of functional PSEN2 studies and the challenges associated with genetic counselling of family members at risk.

摘要

背景

早老素2基因（PSEN2）突变是阿尔茨海默病（AD）的罕见病因。已表明与常染色体显性遗传性AD相关的基因中的致病突变会改变淀粉样前体蛋白（APP）的加工过程，导致β淀粉样蛋白42肽（Aβ42）的量相对增加。

方法与结果

我们报告了一名经神经病理学证实的早发性AD患者，其特征为严重的语言障碍。该患者在PSEN2基因第11外显子上存在一个新的错义突变，为杂合子，该突变导致第393位的缬氨酸预测性地被甲硫氨酸取代，这是一个保守残基。然而，PSEN2 V393M cDNA的体外表达并未导致可检测到的分泌型Aβ42/40肽比率增加。在检测的384名对照个体中未发现该突变。