Müller Ulrich, Winter Pia, Bolender Claus, Nolte Dagmar
Institute of Human Genetics, Justus Liebig University, Giessen, Germany.
Gemeinschaftspraxis, Schlüchtern, Germany.
J Alzheimers Dis. 2014;42(1):109-13. doi: 10.3233/JAD-140399.
Mutations in the gene PSEN2 are a rare cause of early onset Alzheimer's disease (EOAD). PSEN2 sequence variants are often only found in one patient and pathogenicity cannot be formally documented. Here we describe a previously unrecognized sequence change (c.376G>A) in PSEN2 in an EOAD patient and her likewise affected mother. This change results in the exchange of amino acid glutamic acid (E) by lysine (K) at position 126 of the protein (p.E126K). Pathogenicity of the mutation is shown by segregation with disease, evolutionary conservation of E126, and in silico analysis of the mutation.
PSEN2基因的突变是早发性阿尔茨海默病（EOAD）的罕见病因。PSEN2序列变异通常仅在一名患者中发现，其致病性无法得到正式记录。在此，我们描述了一名早发性阿尔茨海默病患者及其同样患病的母亲中PSEN2基因一种先前未被识别的序列变化（c.376G>A）。这种变化导致蛋白质第126位的氨基酸谷氨酸（E）被赖氨酸（K）取代（p.E126K）。该突变的致病性通过与疾病的共分离、E126的进化保守性以及对该突变的计算机分析得以证实。
