Kowalska Anna, Wender Mieczyslaw, Florczak Jolanta, Pruchnik-Wolinska Danuta, Modestowicz Renata, Szczech Józef, Rossa Grzegorz, Kozubski Wojciech
Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszyńska 32, 60-479 Poznań.
J Appl Genet. 2003;44(2):231-4.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and personality changes. Pathological hallmarks of AD are: deposition of amyloid plaques and neurofibrillary tangles in the brain, accompanied by neuronal and synaptic loss. The genetic background of AD is heterogeneous and strongly depends on the form of the disease. In most of the families with early-onset AD (EOAD) (10% of the total population of patients), the disease segregates as an autosomal dominant fully penetrant trait. To date, some missense mutations in three genes encoding the amyloid precursor protein, presenilin 1 (PS1) and 2 (PS2) have been found to cause familial EOAD. We screened for mutations in the presenilin genes in a sample of 55 patients with familial or sporadic form of EOAD from the Poznan region. We found 4 missense mutations in the PS1 gene: A246E in exon 7, P267L in exon 8, E318G in exon 9, and L424R in exon 12 among 5 unrelated patients. The frequency of PS1 mutations was 11% (5 of 55) in the whole sample of the patients with EOAD or 50% (3 of 6) if the analysis was restricted to familial cases with a positive history of dementia in the patient's family.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为记忆丧失和性格改变。AD的病理特征包括：大脑中淀粉样斑块和神经原纤维缠结的沉积，同时伴有神经元和突触的丧失。AD的遗传背景具有异质性，且在很大程度上取决于疾病的形式。在大多数早发性AD（EOAD）家族（占患者总数的10%）中，该疾病作为一种常染色体显性完全显性性状进行遗传。迄今为止，已发现编码淀粉样前体蛋白、早老素1（PS1）和2（PS2）的三个基因中的一些错义突变会导致家族性EOAD。我们在来自波兹南地区的55例家族性或散发性EOAD患者样本中筛查了早老素基因中的突变。我们在5例无亲缘关系的患者中发现了PS1基因的4个错义突变：外显子7中的A246E、外显子8中的P267L、外显子9中的E318G以及外显子12中的L424R。在EOAD患者的整个样本中，PS1突变的频率为11%（55例中的5例）；如果分析仅限于患者家族中有痴呆症阳性病史的家族性病例，则该频率为50%（6例中的3例）。
